Endo Flashcards
Q: What is the most common cause of acromegaly?
A: A pituitary adenoma, which causes excess growth hormone in over 95% of cases.
Q: What are some features of acromegaly?
Coarse facial appearance
Spade-like hands
Increase in shoe size
Large tongue
Prognathism
Interdental spaces
Excessive sweating and oily skin
Features of pituitary tumour (hypopituitarism, headaches, bitemporal hemianopia)
Raised prolactin (1/3 of cases) leading to galactorrhoea
Q: What causes the excessive sweating and oily skin in acromegaly?
A: Sweat gland hypertrophy.
Q: What are some complications of acromegaly?
Hypertension
Diabetes (in more than 10% of patients)
Cardiomyopathy
Colorectal cancer
Q: Why are growth hormone (GH) levels not diagnostic for acromegaly?
A: GH levels vary throughout the day, making them unreliable for diagnosis.
Q: What is the first-line test for acromegaly diagnosis?
A: Serum IGF-1 levels, which have overtaken the oral glucose tolerance test (OGTT) with serial GH measurements.
Q: When should the oral glucose tolerance test (OGTT) be used in acromegaly diagnosis?
A: The OGTT is recommended to confirm the diagnosis if IGF-1 levels are raised.
Q: How is serum IGF-1 used in the management of acromegaly?
A: Serum IGF-1 can also be used to monitor disease progression.
Q: What happens during an oral glucose tolerance test (OGTT) in normal patients versus acromegaly patients?
In normal patients, GH is suppressed to < 2 µg/L with hyperglycemia.
In acromegaly, GH is not suppressed, and the test may also demonstrate impaired glucose tolerance, which is associated with acromegaly.
Q: What imaging modality is used to detect a pituitary tumour in acromegaly?
A: A pituitary MRI may demonstrate a pituitary tumour.
Q: What is the first-line treatment for acromegaly in the majority of patients?
A: Trans-sphenoidal surgery.
Q: What are the medication options for acromegaly if surgery is unsuccessful or the pituitary tumour is inoperable?
Somatostatin analogues (e.g., octreotide)
Pegvisomant (GH receptor antagonist)
Dopamine agonists (e.g., bromocriptine)
External irradiation
Q: What is the most common cause of primary hypoadrenalism in the UK?
A: Autoimmune destruction of the adrenal glands, known as Addison’s disease, which accounts for 80% of cases.
Q: What are the key features of Addison’s disease?
Lethargy
Weakness
Anorexia
Nausea & vomiting
Weight loss
‘Salt-craving’
Hyperpigmentation (especially in palmar creases)
Vitiligo
Loss of pubic hair in women
Hypotension
Hypoglycaemia
Hyponatraemia and hyperkalaemia
In crisis: collapse, shock, pyrexia
Q: Why does hyperpigmentation occur in Addison’s disease?
A: ACTH is derived from proopiomelanocortin (POMC), which is also cleaved to produce melanocyte-stimulating hormones (MSH). MSH stimulates melanocytes to produce more melanin, leading to hyperpigmentation.
Q: How does Addison’s disease differ from secondary adrenal insufficiency regarding pigmentation?
A: Primary Addison’s disease is associated with hyperpigmentation, whereas secondary adrenal insufficiency is not.
Q: What are the primary causes of hypoadrenalism?
Tuberculosis
Metastases (e.g., bronchial carcinoma)
Meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
Antiphospholipid syndrome
Q: What are the secondary causes of hypoadrenalism?
A: Pituitary disorders, such as tumours, irradiation, or infiltration.
Q: What is an additional cause of hypoadrenalism unrelated to disease processes?
A: Exogenous glucocorticoid therapy.
Q: What is the definitive investigation for Addison’s disease?
A: The ACTH stimulation test (short Synacthen test), where plasma cortisol is measured before and 30 minutes after administering Synacthen 250 µg IM.
Q: What can be used if an ACTH stimulation test is not readily available (e.g., in primary care)?
A 9 am serum cortisol test can be useful:
500 nmol/L makes Addison’s disease very unlikely
< 100 nmol/L is definitely abnormal
100-500 nmol/L should prompt an ACTH stimulation test
Q: What are the associated electrolyte abnormalities seen in about one-third of undiagnosed Addison’s disease patients?
Hyperkalaemia
Hyponatraemia
Hypoglycaemia
Metabolic acidosis
Q: What is the usual treatment for Addison’s disease?
A: Patients are typically given both glucocorticoid and mineralocorticoid replacement therapy.
Q: What glucocorticoid and mineralocorticoid are commonly used in Addison’s disease treatment?
Hydrocortisone (usually in 2 or 3 divided doses, typically 20-30 mg per day, with most given in the first half of the day)
Fludrocortisone
Q: How should glucocorticoid and mineralocorticoid doses be adjusted during intercurrent illness?
A: The glucocorticoid dose should be doubled, while the fludrocortisone dose remains the same.
Q: What are common causes of Addisonian crisis?
Sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s disease, Hypopituitarism)
Adrenal haemorrhage (e.g., Waterhouse-Friderichsen syndrome, fulminant meningococcemia)
Steroid withdrawal
Q: What is the initial management of Addisonian crisis?
Hydrocortisone 100 mg IM or IV
1 litre normal saline infused over 30-60 minutes, or with dextrose if hypoglycaemic
Q: How should hydrocortisone be administered during Addisonian crisis?
A: Continue hydrocortisone every 6 hours until the patient is stable.
Q: Why is fludrocortisone not required during an Addisonian crisis?
A: High cortisol exerts a weak mineralocorticoid action, so fludrocortisone is not necessary.
Q: When can oral replacement therapy be started in Addisonian crisis?
A: Oral replacement may begin after 24 hours and should be reduced to maintenance over 3-4 days.
Q: What is the cause of Bartter’s syndrome?
A: Bartter’s syndrome is an inherited (usually autosomal recessive) condition causing severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle.
Q: How is Bartter’s syndrome different from other causes of hypokalaemia like Conn’s, Cushing’s, and Liddle’s syndrome?
A: Bartter’s syndrome is associated with normotension, unlike other endocrine causes of hypokalaemia, which are associated with hypertension.
Q: How do loop diuretics, like furosemide, relate to Bartter’s syndrome?
A: Loop diuretics inhibit NKCC2, and Bartter’s syndrome can be thought of as similar to taking large doses of furosemide, as it also impairs chloride absorption at the same transporter.
Q: What are the common features of Bartter’s syndrome?
Usually presents in childhood (e.g., failure to thrive)
Polyuria and polydipsia
Hypokalaemia
Normotension
Weakness
Q: What is Carbimazole used for?
A: Carbimazole is used in the management of thyrotoxicosis.
Q: How is Carbimazole typically administered in the treatment of thyrotoxicosis?
A: It is typically given in high doses for 6 weeks until the patient becomes euthyroid, after which the dose is reduced.
Q: What are the adverse effects of Carbimazole?
Agranulocytosis
It crosses the placenta but may be used in low doses during pregnancy.
Q: How does hypomagnesaemia affect calcium levels?
A: Hypomagnesaemia can cause hypocalcaemia and render patients unresponsive to treatment with calcium and vitamin D supplementation.
Q: What is the role of magnesium in relation to PTH?
A: Magnesium is required for both PTH secretion and its action on target tissues.
Q: Where is magnesium stored in the body?
A: Magnesium is the fourth most abundant cation in the body, with 50% stored in bone and the remainder in muscle, soft tissues, and extracellular fluid.
Q: How do magnesium and calcium interact at a cellular level?
A: Decreased magnesium affects the permeability of cellular membranes to calcium, resulting in hyperexcitability.
Q: What is congenital adrenal hyperplasia (CAH)?
A: CAH refers to a group of autosomal recessive disorders that impair adrenal steroid biosynthesis, leading to cortisol deficiency and compensatory overproduction of adrenocorticotropic hormone (ACTH), which increases adrenal androgen production.
Q: What is the most common cause of CAH?
A: 21-hydroxylase deficiency (90%), which impairs the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, leading to cortisol deficiency and excess androgen production.
Q: What are other causes of CAH?
11-beta hydroxylase deficiency (5%), leading to hypertension due to excess deoxycorticosterone.
17-hydroxylase deficiency (very rare), resulting in mineralocorticoid excess with low androgen and estrogen levels.
Q: What are the clinical features of CAH?
Virilization: Female infants may present with ambiguous genitalia; male infants appear normal at birth.
Salt-wasting crisis: Occurs in 75% of cases with 21-hydroxylase deficiency, characterized by dehydration, hypotension, and electrolyte imbalances.
Precocious puberty: Early development of secondary sexual characteristics.
Infertility: Due to hormonal imbalances.
Height and growth abnormalities: Accelerated growth rates initially, but shorter adult stature.
Q: How is CAH managed?
Glucocorticoid replacement to reduce ACTH levels and minimize adrenal androgen production.
Fludrocortisone is prescribed in cases of mineralocorticoid deficiency.
Q: What are the features of 21-hydroxylase deficiency in CAH?
Virilization of female genitalia
Precocious puberty in males
60-70% of patients have a salt-losing crisis at 1-3 weeks of age
Q: What are the features of 11-beta hydroxylase deficiency in CAH?
Virilization of female genitalia
Precocious puberty in males
Hypertension
Hypokalaemia
Q: What are the features of 17-hydroxylase deficiency in CAH?
Non-virilizing in females
Inter-sex in males
Hypertension
Q: What are the clinical features of congenital hypothyroidism?
Prolonged neonatal jaundice
Delayed mental and physical milestones
Short stature
Puffy face and macroglossia
Hypotonia
Q: How are children screened for congenital hypothyroidism?
A: Children are screened at 5-7 days using the heel prick test.
Q: What are some common side effects of glucocorticoids?
Endocrine: Impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia, Cushing’s syndrome (moon face, buffalo hump, striae)
Musculoskeletal: Osteoporosis, proximal myopathy, avascular necrosis of the femoral head
Immunosuppression: Increased susceptibility to infections, reactivation of tuberculosis
Psychiatric: Insomnia, mania, depression, psychosis
Gastrointestinal: Peptic ulceration, acute pancreatitis
Ophthalmic: Glaucoma, cataracts
Other: Suppression of growth in children, intracranial hypertension, neutrophilia
Q: What are the side effects of mineralocorticoids?
A: Fluid retention and hypertension.
Q: What should be done with corticosteroid doses during intercurrent illness?
A: Patients on long-term steroids should have their doses doubled during intercurrent illness.
Q: Why should corticosteroids not be withdrawn abruptly in patients on long-term therapy?
A: Abrupt withdrawal may precipitate an Addisonian crisis, as prolonged use suppresses natural production of endogenous steroids.
Q: What are the guidelines for gradual withdrawal of systemic corticosteroids?
Gradual withdrawal should be considered if patients have:
Received more than 40mg prednisolone daily for more than one week
Received more than 3 weeks of treatment
Recently received repeated courses
Q: What are the endocrine side effects of glucocorticoids?
Impaired glucose regulation
Increased appetite/weight gain
Hirsutism
Hyperlipidaemia
Q: What are the signs of Cushing’s syndrome caused by glucocorticoids?
Moon face
Buffalo hump
Striae
Q: What are the musculoskeletal side effects of glucocorticoids?
Osteoporosis
Proximal myopathy
Avascular necrosis of the femoral head
Q: What are the immunosuppression-related side effects of glucocorticoids?
Increased susceptibility to severe infection
Reactivation of tuberculosis
Q: What psychiatric side effects can glucocorticoids cause?
Insomnia
Mania
Depression
Psychosis
Q: What gastrointestinal side effects are associated with glucocorticoids?
Peptic ulceration
Acute pancreatitis
Q: What ophthalmic side effects are caused by glucocorticoids?
Glaucoma
Cataracts
Q: What dermatological side effect is common with glucocorticoid use?
Acne
Q: What are the effects of glucocorticoids on growth in children?
A: Suppression of growth
Q: What are the neurological side effects of glucocorticoids?
A: Intracranial hypertension and neutrophilia
Q: What are the mineralocorticoid side effects?
Fluid retention
Hypertension
Q: What is the most common cause of exogenous Cushing’s syndrome?
A: Glucocorticoid therapy (steroid use) is the most common cause of exogenous Cushing’s syndrome.
Q: What are the ACTH-dependent causes of Cushing’s syndrome?
Cushing’s disease (80%): Pituitary tumor secreting ACTH, leading to adrenal hyperplasia
Ectopic ACTH production (5-10%): Often caused by small cell lung cancer
Q: What are the ACTH-independent causes of Cushing’s syndrome?
Iatrogenic (steroids)
Adrenal adenoma (5-10%)
Adrenal carcinoma (rare)
Carney complex: A syndrome that includes cardiac myxoma
Micronodular adrenal dysplasia (very rare)
Q: What is pseudo-Cushing’s syndrome, and what causes it?
A: Pseudo-Cushing’s syndrome mimics Cushing’s syndrome, often caused by alcohol excess or severe depression. It can cause false positive results in the dexamethasone suppression test or 24-hour urinary free cortisol.
Q: How can pseudo-Cushing’s syndrome be differentiated from true Cushing’s syndrome?
A: The insulin stress test can be used to differentiate pseudo-Cushing’s syndrome from true Cushing’s syndrome.
Q: What general lab findings are consistent with Cushing’s syndrome?
Hypokalaemic metabolic alkalosis
Impaired glucose tolerance
Very low potassium levels (especially in ectopic ACTH secretion, e.g., small cell lung cancer)
Q: What are the three most commonly used tests to confirm Cushing’s syndrome?
Overnight (low-dose) dexamethasone suppression test
24-hour urinary free cortisol
Bedtime salivary cortisol
Q: How does the overnight (low-dose) dexamethasone suppression test work in Cushing’s syndrome?
A: In Cushing’s syndrome, the morning cortisol spike is not suppressed by dexamethasone.
Q: What are the first-line tests for localising the cause of Cushing’s syndrome?
9am and midnight plasma ACTH (and cortisol) levels.
Suppressed ACTH suggests a non-ACTH dependent cause (e.g., adrenal adenoma).
Elevated ACTH suggests an ACTH-dependent cause (e.g., Cushing’s disease or ectopic ACTH).
Q: How is the high-dose dexamethasone suppression test interpreted?
Not suppressed cortisol, suppressed ACTH: Likely adrenal cause (e.g., adrenal adenoma)
Suppressed cortisol and ACTH: Likely Cushing’s disease (pituitary adenoma)
Not suppressed cortisol and ACTH: Likely ectopic ACTH syndrome
Q: What does a CRH stimulation test help determine in Cushing’s syndrome diagnosis?
Pituitary source: Cortisol levels rise after CRH stimulation
Ectopic/adrenal source: No change in cortisol levels after CRH stimulation
Q: When is petrosal sinus sampling of ACTH used in Cushing’s syndrome?
A: It may be used to differentiate between pituitary and ectopic ACTH secretion.
Q: What test is used to differentiate between true Cushing’s syndrome and pseudo-Cushing’s syndrome?
A: The insulin stress test.
Q: What are the common features of diabetic ketoacidosis (DKA) in Type 1 Diabetes Mellitus (T1DM)?
Abdominal pain
Polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell)
Q: What are the key investigations for diagnosing Type 1 Diabetes Mellitus (T1DM)?
Urine dip for glucose and ketones
Fasting glucose and random glucose
HbA1c (less useful for T1DM)
C-peptide levels (typically low in T1DM)
Diabetes-specific autoantibodies (e.g., anti-GAD, ICA, IAA, IA-2A)
Q: What are the diagnostic criteria for Type 1 Diabetes Mellitus (T1DM) if the patient is symptomatic?
Fasting glucose ≥ 7.0 mmol/l
Random glucose ≥ 11.1 mmol/l (or after 75g oral glucose tolerance test)
Q: What are the diagnostic criteria for Type 1 Diabetes Mellitus (T1DM) if the patient is asymptomatic?
The above criteria (fasting ≥ 7.0 mmol/l or random ≥ 11.1 mmol/l) must be demonstrated on two separate occasions.
Q: What are the typical age, speed of onset, and features for Type 1 Diabetes Mellitus (T1DM) compared to Type 2 Diabetes Mellitus (T2DM)?
Q: What are some key features that suggest Type 1 Diabetes (T1DM) in adults, according to NICE guidelines?
Ketosis
Rapid weight loss
Age of onset below 50 years
BMI below 25 kg/m²
Personal and/or family history of autoimmune disease
Q: When should further investigation (C-peptide and/or diabetes-specific autoantibodies) be considered in adults suspected of Type 1 Diabetes (T1DM)?
If T1DM is suspected but the clinical presentation includes atypical features such as:
Age > 50 years
BMI ≥ 25 kg/m²
Slow evolution of hyperglycaemia or long prodrome
Q: In which cases is further testing for Type 1 Diabetes (T1DM) not required in patients suspected of Type 2 Diabetes (T2DM)?
If the patient is over 40 years old
Responds well to oral hypoglycaemic agents
No need for further testing for T1DM unless there is doubt
Q: What is the approach for diagnosing Type 1 Diabetes (T1DM) in a 15-year-old with weight loss, lethargy, and ketones and glucose in the urine?
Diagnosis: T1DM is confirmed with random serum glucose of 14 mmol/L (no further investigations needed).
Q: What would be the next steps in diagnosing Type 1 Diabetes (T1DM) in a 38-year-old obese man with polyuria and a random glucose of 12.5 mmol/L?
Perform C-peptide levels and diabetes-specific autoantibodies due to atypical features (obesity, intermediate age).
Q: How would you approach a 52-year-old woman with polyuria, polydipsia, and ketones in the urine, but with a BMI of 23 kg/m²?
T1DM is suspected due to symptoms, but due to age, further testing with C-peptide levels and diabetes-specific autoantibodies is recommended.
Q: When is HbA1c used for diagnosing Type 2 Diabetes Mellitus (T2DM), and what are the thresholds?
HbA1c ≥ 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
HbA1c < 48 mmol/mol (6.5%) does not exclude diabetes
In asymptomatic patients, the test must be repeated for confirmation.
Q: What conditions may affect the accuracy of HbA1c testing for diagnosing diabetes?
Haemoglobinopathies
Haemolytic anaemia
Untreated iron deficiency anaemia
Suspected gestational diabetes
Children
HIV
Chronic kidney disease
Medications that may cause hyperglycaemia (e.g., corticosteroids)
Q: What is the diagnostic criterion for Impaired Fasting Glucose (IFG)?
Fasting glucose ≥ 6.1 but < 7.0 mmol/l.
Q: What is the diagnostic criterion for Impaired Glucose Tolerance (IGT)?
Fasting glucose < 7.0 mmol/l and
OGTT 2-hour value ≥ 7.8 but < 11.1 mmol/l.
Q: What is the recommended follow-up for someone with Impaired Fasting Glucose (IFG)?
An Oral Glucose Tolerance Test (OGTT) should be offered to rule out diabetes.
A result between 7.8 and 11.1 mmol/l indicates Impaired Glucose Tolerance (IGT), not diabetes.
Q: What is the first-line drug for managing Type 2 diabetes?
A: Metformin, which increases insulin sensitivity and decreases hepatic gluconeogenesis.
Q: What drugs are commonly used in the management of diabetes?
Insulin: Required for Type 1 DM and some poorly controlled Type 2 DM patients.
Metformin: First-line for T2DM.
Sulfonylureas: Stimulate insulin secretion.
GLP-1 agonists and SGLT-2 inhibitors: Incretin mimetics and glucose reabsorption inhibitors.
Q: What is the role of GLP-1 in diabetes mellitus?
A: GLP-1 (glucagon-like peptide-1) is a hormone released by the small intestine in response to oral glucose. It enhances insulin secretion and inhibits glucagon secretion, contributing to the incretin effect. In Type 2 diabetes (T2DM), this effect is impaired.
Q: What are GLP-1 mimetics?
A: GLP-1 mimetics, such as exenatide and liraglutide, are drugs that mimic the action of GLP-1. They increase insulin secretion, inhibit glucagon secretion, and often result in weight loss, making them different from many other diabetes medications.
Q: How does exenatide work and when is it administered?
A: Exenatide is a GLP-1 mimetic that is administered by subcutaneous injection. It should be given 60 minutes before meals, twice daily. It helps increase insulin secretion and suppress glucagon secretion.
Q: What are the advantages of GLP-1 mimetics like exenatide and liraglutide?
A: GLP-1 mimetics typically result in weight loss and are used in combination with other drugs like metformin or sulfonylureas. They are beneficial for patients with high BMI and may help with other comorbidities related to weight.
Q: What are the major adverse effects of GLP-1 mimetics?
A: The main adverse effects include nausea and vomiting. Exenatide has also been associated with severe pancreatitis in some patients.
Q: When might NICE recommend adding exenatide to a treatment regimen?
NICE suggests adding exenatide if:
BMI ≥ 35 kg/m² in people of European descent with weight-related problems, or
BMI < 35 kg/m², and insulin is not acceptable due to occupational reasons or weight loss benefits.
Q: What is the NICE guideline for the ongoing prescription of GLP-1 mimetics?
A: NICE recommends that GLP-1 mimetics should only continue if the patient achieves a >11 mmol/mol (1%) reduction in HbA1c and a 3% weight loss after 6 months.
Q: What are DPP-4 inhibitors, and how do they work?
A: DPP-4 inhibitors, such as vildagliptin and sitagliptin, increase levels of incretins (GLP-1 and GIP) by inhibiting their breakdown, enhancing insulin secretion and suppressing glucagon without causing weight gain.
Q: What are the advantages of DPP-4 inhibitors?
A: DPP-4 inhibitors are well tolerated, do not increase the incidence of hypoglycaemia, and do not cause weight gain, making them a preferable option for patients who need to avoid these side effects.
Q: How often should HbA1c be monitored in adults with Type 1 diabetes?
A: HbA1c should be monitored every 3-6 months. The target for adults is a level of 48 mmol/mol (6.5%) or lower, but individual factors like daily activities and history of hypoglycaemia should be considered.
Q: How often should blood glucose be self-monitored in Type 1 diabetes?
A: Blood glucose should be tested at least 4 times a day, including before each meal and before bed. More frequent monitoring is recommended during illness, increased hypoglycaemia, exercise, pregnancy, or breastfeeding.
Q: What are the recommended blood glucose targets for adults with Type 1 diabetes?
5-7 mmol/l upon waking
4-7 mmol/l before meals at other times of the day
Q: What insulin regimen is recommended for adults with Type 1 diabetes?
A: A multiple daily injection basal-bolus insulin regimen is preferred, rather than a twice-daily mixed insulin regimen. Insulin detemir twice daily is the regime of choice, with once-daily insulin glargine or insulin detemir as alternatives.
Q: What type of insulin is recommended for mealtime insulin replacement in Type 1 diabetes?
A: Rapid-acting insulin analogues should be used before meals, rather than rapid-acting soluble human or animal insulins.
Q: When should metformin be considered in Type 1 diabetes management?
A: Metformin should be considered if the patient’s BMI is ≥ 25 kg/m².
Q: What is the target HbA1c for a patient on lifestyle changes or metformin for Type 2 diabetes?
A: The target HbA1c is 48 mmol/mol (6.5%).
Q: When should a second drug be added in the management of Type 2 diabetes?
A: A second drug should be added if the HbA1c rises to 58 mmol/mol (7.5%).
Q: What is the target HbA1c for patients with Type 2 diabetes on lifestyle changes or metformin?
A: The target is 48 mmol/mol (6.5%). For those on drugs that cause hypoglycaemia (e.g., sulfonylureas), the target is 53 mmol/mol (7.0%).
Q: What is the first-line drug for Type 2 diabetes?
A: Metformin is the first-line drug of choice.
Q: When should SGLT-2 inhibitors be added to treatment for Type 2 diabetes?
A: SGLT-2 inhibitors should be added if the patient has a high risk of cardiovascular disease, established cardiovascular disease, or chronic heart failure. Metformin should be established before introducing an SGLT-2 inhibitor.
Q: What should be done if metformin is contraindicated in Type 2 diabetes management?
A: If the patient has cardiovascular disease or chronic heart failure, use SGLT-2 monotherapy. If not, consider DPP-4 inhibitors, pioglitazone, or sulfonylureas.
Q: What are the second-line therapy options if HbA1c targets are not met?
Options include:
Metformin + DPP-4 inhibitor
Metformin + pioglitazone
Metformin + sulfonylurea
Metformin + SGLT-2 inhibitor (if criteria met)
Q: What is the third-line therapy if dual therapy fails?
Metformin + DPP-4 inhibitor + sulfonylurea
Metformin + pioglitazone + sulfonylurea
Metformin + (pioglitazone, sulfonylurea, or DPP-4 inhibitor) + SGLT-2 inhibitor (if criteria met)
Q: When should GLP-1 mimetics be considered in Type 2 diabetes?
A: GLP-1 mimetics should be added if BMI ≥ 35 kg/m² with obesity-related issues or if BMI < 35 kg/m² with potential benefits for weight loss or insulin therapy implications.
Q: What is the recommended starting insulin therapy for Type 2 diabetes?
A: Start with human NPH insulin (isophane, intermediate-acting) at bedtime or twice daily according to need, while continuing metformin.
Q: What blood pressure target is recommended for patients with Type 2 diabetes under age 80?
A: The target blood pressure is 140/90 mmHg in the clinic and 135/85 mmHg using ABPM or HBPM.
Q: When should statins be prescribed for Type 2 diabetes patients?
A: Statins (atorvastatin 20mg) should be prescribed if the patient has a 10-year cardiovascular risk > 10% (using QRISK2).
Q: What should patients with Type 1 diabetes do if they are sick?
Do not stop insulin to prevent diabetic ketoacidosis.
Check blood glucose every 1-2 hours, including through the night.
Consider checking blood or urine ketone levels regularly.
Maintain normal meal patterns if possible.
If appetite is reduced, replace meals with carbohydrate-containing drinks (e.g., milk, milkshakes, fruit juices, sugary drinks).
Aim for at least 3L (5 pints) of fluid a day to prevent dehydration.
Q: What should patients with Type 2 diabetes do during illness?
Temporarily stop some oral hypoglycaemics.
Restart medications once the person feels better and is eating and drinking for 24-48 hours.
Q: What should patients with Type 2 diabetes do if they are on metformin during illness?
A: Stop metformin if there is a risk of dehydration to reduce the risk of lactic acidosis.
Q: What is the advice for patients with Type 2 diabetes on sulfonylureas during illness?
A: Stop sulfonylureas if there is a risk of hypoglycaemia during illness.
Q: What should be done for patients on SGLT-2 inhibitors during an acute illness?
Check for ketones.
Stop SGLT-2 inhibitors if acutely unwell or at risk of dehydration, due to the risk of euglycaemic diabetic ketoacidosis (DKA).
Q: What should patients on GLP-1 receptor agonists do during illness?
A: Stop treatment if there is a risk of dehydration to reduce the risk of acute kidney injury (AKI).
Q: What should patients on insulin therapy do during illness?
A: Do not stop insulin therapy, as it is essential to prevent diabetic ketoacidosis.
Q: What is the recommendation for monitoring blood glucose during illness in patients with Type 1 or Type 2 diabetes?
A: Monitor blood glucose more frequently as necessary, particularly when ill or when there are changes in eating patterns or hydration.
Q: What are the two main factors that contribute to diabetic foot disease?
Neuropathy: Loss of protective sensation (e.g., not noticing a stone in the shoe), Charcot’s arthropathy, dry skin.
Peripheral arterial disease: Diabetes is a risk factor for both macro and microvascular ischaemia.
Q: What are the typical presentations of diabetic foot disease?
Neuropathy: Loss of sensation.
Ischaemia: Absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication.
Complications: Calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, gangrene.
Q: How should diabetic foot disease be screened?
Ischaemia screening: Palpate for dorsalis pedis and posterior tibial pulses.
Neuropathy screening: Use a 10 g monofilament on various parts of the sole of the foot.
Q: What is the recommended frequency for screening diabetic foot disease?
A: All patients with diabetes should be screened for diabetic foot disease at least annually.
Q: What are the risk categories for diabetic foot disease, and what defines them?
Low risk: No risk factors except callus alone.
Moderate risk: Deformity, neuropathy, or non-critical limb ischaemia.
High risk: Previous ulceration, amputation, renal replacement therapy, neuropathy and non-critical limb ischaemia together, neuropathy with callus/deformity, or non-critical limb ischaemia with callus/deformity.
Q: How should patients in moderate or high-risk categories for diabetic foot disease be managed?
A: All moderate or high-risk patients should be followed up regularly by the local diabetic foot centre.
Q: What are the main causes of diabetic ketoacidosis (DKA)?
Uncontrolled lipolysis, leading to excess free fatty acids that are converted into ketone bodies.
Common precipitating factors: infection, missed insulin doses, and myocardial infarction.
Q: What are the common clinical features of DKA?
Abdominal pain
Polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (“pear drops” smell)
Q: What are the key principles in the management of DKA?
Fluid replacement: Most patients are depleted by 5-8 liters, starting with isotonic saline.
Insulin: IV infusion at 0.1 unit/kg/hour. Once blood glucose is < 14 mmol/l, start dextrose infusion (10% dextrose at 125 mls/hr).
Electrolyte correction: Serum potassium is often high initially but may drop with treatment, requiring potassium replacement.
Long-acting insulin: Should continue, but short-acting insulin should be stopped.
Q: What is the JBDS example fluid replacement regime for a patient with a systolic BP of 90mmHg and over?
0.9% sodium chloride 1L over 1st hour
0.9% sodium chloride 1L with potassium chloride over next 2 hours
Continue 0.9% sodium chloride with potassium chloride at 1L every 2-4 hours as per need.
Q: What are the JBDS potassium guidelines for the first 24 hours in DKA management?
Potassium > 5.5 mmol/L: Nil replacement.
Potassium 3.5-5.5 mmol/L: Add 40 mmol of potassium to the infusion.
Potassium < 3.5 mmol/L: Senior review for additional potassium replacement
Q: What are the criteria for DKA resolution?
pH > 7.3
Blood ketones < 0.6 mmol/L
Bicarbonate > 15.0 mmol/L
Both ketonaemia and acidosis should resolve within 24 hours.
Q: What are the potential complications of DKA?
Gastric stasis
Thromboembolism
Arrhythmias from hyperkalaemia/iatrogenic hypokalaemia
Iatrogenic complications (e.g., cerebral oedema, hypokalaemia, hypoglycaemia)
Acute respiratory distress syndrome
Acute kidney injury
(Cerebral oedema is especially a risk in children/young adults and requires close monitoring.)
Q: What is the typical presentation of peripheral diabetic neuropathy?
Sensory loss, typically in a “glove and stocking” distribution.
The lower legs are affected first due to the length of the sensory neurons.
Painful diabetic neuropathy is common in clinical practice.
Q: How is painful diabetic neuropathy managed?
First-line treatment:
Amitriptyline, duloxetine, gabapentin, or pregabalin.
If the first-line drugs are ineffective: Try another of the 3 first-line options.
Rescue therapy: Tramadol for exacerbations of neuropathic pain.
Topical treatment: Capsaicin for localized neuropathic pain (e.g., post-herpetic neuralgia).
Pain management clinics may be helpful for patients with resistant problems.
Q: What is the management for gastrointestinal autonomic neuropathy in diabetic patients?
Gastroparesis (delayed gastric emptying):
Symptoms: erratic blood glucose control, bloating, vomiting.
Management: Metoclopramide, domperidone, or erythromycin (prokinetic agents).
Chronic diarrhoea: Often occurs at night.
Gastro-oesophageal reflux disease (GERD): Caused by decreased lower esophageal sphincter (LES) pressure.
Q: What is Androgen Insensitivity Syndrome?
Karyotype: 46 XY (genotypically male).
Cause: X-linked recessive condition with a defect in the androgen receptor, resulting in resistance to testosterone.
Phenotype: Female external genitalia, rudimentary vagina, and testes (no uterus).
Hormone levels: Elevated testosterone, oestrogen, and LH.
Q: What is 5-α reductase deficiency?
Karyotype: 46 XY (genotypically male).
Cause: Autosomal recessive condition, inability to convert testosterone to dihydrotestosterone (DHT).
Phenotype: Ambiguous genitalia at birth, common hypospadias.
Virilization: Occurs at puberty due to increased DHT levels.
Q: What is Male pseudohermaphroditism?
Karyotype: 46 XY.
Cause: The individual has testes, but external genitalia are female or ambiguous.
Example: Can be secondary to androgen insensitivity syndrome.
Q: What is Female pseudohermaphroditism?
Karyotype: 46 XX.
Cause: The individual has ovaries, but external genitalia are male or ambiguous.
Example: Can be secondary to congenital adrenal hyperplasia.
Q: What is True hermaphroditism?
Karyotype: 46 XX or 47 XXY.
Cause: A rare condition where both ovarian and testicular tissue are present.
Phenotype: Both male and female reproductive tissues.
Q: What factors affect HbA1c levels?
Red blood cell lifespan: Longer lifespan = higher HbA1c.
Average blood glucose concentration: Higher blood glucose = higher HbA1c.
Q: What conditions cause lower-than-expected HbA1c levels due to reduced red blood cell lifespan?
Sickle-cell anaemia
G6PD deficiency
Hereditary spherocytosis
Haemodialysis
Q: What conditions cause higher-than-expected HbA1c levels due to increased red blood cell lifespan?
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
Q: How often should HbA1c be checked?
HbA1c should be checked every 3-6 months until stable, then 6 monthly.
Q: What is Graves’ disease?
Graves’ disease is an autoimmune thyroid disorder where the body produces IgG antibodies against the TSH receptor.
It is the most common cause of thyrotoxicosis, typically affecting women aged 30-50 years.
Q: What are the typical features of thyrotoxicosis in Graves’ disease?
Weight loss
Heat intolerance
Tachycardia
Tremor
Increased appetite
Anxiety
Diarrhoea
Q: What are the specific signs of Graves’ disease that differentiate it from other causes of thyrotoxicosis?
Eye signs (30% of patients)
Exophthalmos (bulging eyes)
Ophthalmoplegia (eye movement abnormalities)
Pretibial myxoedema (swelling of the lower legs)
Thyroid acropachy: a triad of
Digital clubbing
Soft tissue swelling of the hands and feet
Periosteal new bone formation
Q: What autoantibodies are typically found in Graves’ disease?
TSH receptor stimulating antibodies (90%)
Anti-thyroid peroxidase antibodies (75%)
Q: What findings are seen on thyroid scintigraphy in Graves’ disease?
Diffuse, homogenous, increased uptake of radioactive iodine.
Q: What are the treatment options for Graves’ disease?
Anti-thyroid drugs (ATDs) like carbimazole
Radioiodine treatment
Surgery
Q: What are the factors that support the use of anti-thyroid drugs (ATDs) in Graves’ disease?
Significant symptoms of thyrotoxicosis
High risk of hyperthyroid complications, such as in elderly patients or those with cardiovascular disease
Q: What is the role of propranolol in the initial treatment of Graves’ disease?
Propranolol is used to block the adrenergic effects of thyrotoxicosis, helping to control symptoms like tachycardia, tremors, and anxiety.
Q: What is the typical management of anti-thyroid drugs (ATDs) in Graves’ disease?
Carbimazole is started at 40 mg and gradually reduced to maintain euthyroidism.
Treatment typically lasts 12-18 months.
The major complication is agranulocytosis.
An alternative regime is block-and-replace, where carbimazole is combined with thyroxine.
Q: What are the advantages of the titration regime compared to the block-and-replace regime in ATD therapy?
Patients on a titration regime (adjusting carbimazole dose to maintain euthyroidism) suffer fewer side effects compared to those on block-and-replace.
Q: What are the indications for radioiodine treatment in Graves’ disease?
Relapse after ATD therapy
Resistance to primary ATD treatment
Q: What are the contraindications for radioiodine treatment in Graves’ disease?
Pregnancy (avoid for 4-6 months after treatment)
Age < 16 years
Thyroid eye disease (relative contraindication, as it may worsen)
Q: What is the expected outcome after radioiodine treatment for Graves’ disease?
The majority of patients will require thyroxine supplementation within 5 years due to hypothyroidism.
Q: What are the indications for growth hormone therapy according to NICE guidance?
Proven growth hormone deficiency
Turner’s syndrome
Prader-Willi syndrome
Chronic renal insufficiency before puberty
Q: How is growth hormone therapy administered?
It is given by subcutaneous injection.
Q: What should be done if there is poor response to growth hormone therapy in the first year?
Treatment should be discontinued if there is a poor response in the first year of therapy.
Q: What are some adverse effects of growth hormone therapy?
Headache
Benign intracranial hypertension
Fluid retention
Q: What is gynaecomastia?
Gynaecomastia is the abnormal growth of breast tissue in males, usually caused by an increased oestrogen:androgen ratio.
Q: What is the main cause of galactorrhoea?
Galactorrhoea is caused by the action of prolactin on the breast tissue, not related to gynaecomastia.
Q: What are the physiological causes of gynaecomastia?
Normal in puberty
Syndromes with androgen deficiency: Kallman’s syndrome, Klinefelter’s syndrome
Q: What are some other causes of gynaecomastia?
Testicular failure (e.g. mumps)
Liver disease
Testicular cancer (e.g. seminoma secreting hCG)
Ectopic tumour secretion
Hyperthyroidism
Haemodialysis
Q: What are some common drug causes of gynaecomastia?
Spironolactone (most common drug cause)
Cimetidine
Digoxin
Cannabis
Finasteride
GnRH agonists (e.g. goserelin, buserelin)
Oestrogens, anabolic steroids
Q: What is Hashimoto’s thyroiditis?
Hashimoto’s thyroiditis (chronic autoimmune thyroiditis) is an autoimmune disorder of the thyroid gland.
It is typically associated with hypothyroidism but may have a transient thyrotoxicosis in the acute phase.
It is 10 times more common in women.
Q: What are the typical features of Hashimoto’s thyroiditis?
Features of hypothyroidism
Goitre: firm, non-tender
Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies present
Q: What are the associations with Hashimoto’s thyroiditis?
Associated with other autoimmune conditions such as:
Coeliac disease
Type 1 diabetes mellitus
Vitiligo
Associated with the development of MALT lymphoma (mucosa-associated lymphoid tissue lymphoma).
Q: What are the two most common causes of hypercalcaemia?
Primary hyperparathyroidism – most common in non-hospitalized patients.
Malignancy – most common in hospitalized patients, including:
PTHrP secretion by tumors (e.g. squamous cell lung cancer)
Bone metastases
Myeloma (due to osteoclastic bone resorption driven by cytokines like IL-1 and TNF)
Q: What is the key investigation for hypercalcaemia?
Parathyroid hormone (PTH) levels – helps to distinguish between primary hyperparathyroidism and malignancy-related hypercalcaemia.
Q: What are some other causes of hypercalcaemia?
Sarcoidosis and other granulomatous diseases (e.g., tuberculosis, histoplasmosis)
Vitamin D intoxication
Acromegaly
Thyrotoxicosis
Milk-alkali syndrome
Drugs:
Thiazides
Calcium-containing antacids
Dehydration
Addison’s disease
Paget’s disease of the bone – hypercalcaemia may occur with prolonged immobilization.
Q: What is the pathophysiology of Hyperosmolar Hyperglycaemic State (HHS)?
Hyperglycaemia → increased serum osmolality → osmotic diuresis → severe volume depletion.
Q: What are common precipitating factors of HHS?
Intercurrent illness
Dementia
Sedative drugs
Q: How does HHS typically present clinically?
Gradual onset (over days) compared to DKA (which presents within hours).
Consequences of volume loss:
Clinical signs of dehydration (e.g., dry mouth, reduced skin turgor)
Polyuria
Polydipsia
Systemic:
Lethargy
Nausea and vomiting
Neurological:
Altered level of consciousness
Focal neurological deficits
Haematological:
Hyperviscosity, which may lead to:
Myocardial infarctions
Stroke
Peripheral arterial thrombosis
Q: What are typical diagnostic findings in HHS?
Hypovolaemia
Marked hyperglycaemia (>30 mmol/L)
Raised serum osmolality (>320 mosmol/kg), calculated as:
2 * Na+ + glucose + urea
No significant hyperketonaemia (<3 mmol/L)
No significant acidosis:
Bicarbonate > 15 mmol/L or pH > 7.3
Acidosis may occur due to lactic acidosis or renal impairment.
Q: What is the initial management for HHS?
Fluid replacement:
IV 0.9% sodium chloride solution, typically at 0.5 - 1 L/hour
Fluid losses are estimated to be 100-220 ml/kg
Potassium levels should be monitored and added if necessary.
Insulin:
Only start when blood glucose stops falling with IV fluids.
Venous thromboembolism prophylaxis:
Patients are at risk due to hyperviscosity.
Q: What are some complications of HHS?
Vascular complications due to hyperviscosity:
Myocardial infarction
Stroke
Q: What are common causes of hypoglycaemia?
Insulinoma: increased ratio of proinsulin to insulin
Self-administration of insulin/sulphonylureas
Liver failure
Addison’s disease
Alcohol: causes exaggerated insulin secretion by affecting pancreatic blood flow
Nesidioblastosis: beta cell hyperplasia
Q: What is the physiological response to hypoglycaemia?
Hormonal response:
Decreased insulin secretion
Increased glucagon secretion
Later, growth hormone and cortisol are released.
Sympathoadrenal response:
Increased catecholamine (adrenergic) and acetylcholine (cholinergic) neurotransmission.
Q: What are the features of hypoglycaemia?
Blood glucose <3.3 mmol/L causes autonomic symptoms (due to glucagon/adrenaline release):
Sweating
Shaking
Hunger
Anxiety
Nausea
Blood glucose <2.8 mmol/L causes neuroglycopenic symptoms (due to inadequate glucose supply to the brain):
Weakness
Vision changes
Confusion
Dizziness
Severe features (uncommon):
Convulsion
Coma
Q: How is hypoglycaemia investigated?
Measure serum insulin and C-peptide levels.
Insulin and C-peptide are released in equimolar amounts, so C-peptide is a marker of endogenous insulin production.
Q: What is the management of hypoglycaemia in the community (e.g., diabetes patients)?
Initially, administer oral glucose (10-20g) in liquid, gel, or tablet form.
Alternatively, use a proprietary quick-acting carbohydrate like GlucoGel or Dextrogel.
HypoKit: A kit with a syringe and vial of glucagon for IM/SC injection may be prescribed for home use.
Q: How is hypoglycaemia managed in a hospital setting?
If the patient is alert, administer quick-acting carbohydrates (as above).
If the patient is unconscious or unable to swallow:
Subcutaneous or intramuscular glucagon.
Alternatively, intravenous 20% glucose solution via a large vein.
Q: What is primary hypoparathyroidism?
Primary hypoparathyroidism is a condition where there is a decreased secretion of parathyroid hormone (PTH).
Commonly seen secondary to thyroid surgery.
It presents with low calcium and high phosphate levels.
Treatment: Alfacalcidol (a form of vitamin D).
Q: What are the main symptoms of hypoparathyroidism?
Tetany: Muscle twitching, cramping, and spasms.
Perioral paraesthesia: Tingling around the mouth.
Trousseau’s sign: Carpal spasm induced by inflating a blood pressure cuff above systolic pressure.
Chvostek’s sign: Tapping over the parotid gland causes facial muscle twitching.
Chronic symptoms: Depression, cataracts.
ECG: Prolonged QT interval due to hypocalcaemia.
Q: What is pseudohypoparathyroidism?
It is a condition where target cells are insensitive to PTH due to an abnormality in a G protein.
Features include low IQ, short stature, and shortened 4th and 5th metacarpals.
Laboratory findings: Low calcium, high phosphate, and high PTH.
Diagnosis: Measure urinary cAMP and phosphate levels after PTH infusion.
In hypoparathyroidism, both cAMP and phosphate levels rise.
In pseudohypoparathyroidism type I, neither rises.
In pseudohypoparathyroidism type II, only cAMP rises.
Q: What is pseudopseudohypoparathyroidism?
It has a similar phenotype to pseudohypoparathyroidism but normal biochemistry.
The term is used to describe patients with the same physical characteristics but without the laboratory abnormalities seen in pseudohypoparathyroidism.
Q: Why is hypoparathyroidism secondary to surgery often classified as primary hypoparathyroidism?
Although it results from a secondary cause (e.g., thyroid surgery), most medical textbooks classify it as primary hypoparathyroidism due to the loss of parathyroid hormone secretion from the glands.
Q: What is the most common cause of primary hypothyroidism?
Hashimoto’s thyroiditis is the most common cause of primary hypothyroidism.
It is an autoimmune disease often associated with insulin-dependent diabetes mellitus (IDDM), Addison’s disease, or pernicious anaemia.
It may cause transient thyrotoxicosis in the acute phase.
Gender prevalence: 5-10 times more common in women.
Q: What are other causes of primary hypothyroidism?
Subacute thyroiditis (de Quervain’s)
Riedel thyroiditis
After thyroidectomy or radioiodine treatment
Drug therapy: e.g., lithium, amiodarone, or anti-thyroid drugs (e.g., carbimazole)
Dietary iodine deficiency
Q: What is secondary hypothyroidism?
Secondary hypothyroidism is much rarer and occurs due to pituitary failure, where the pituitary gland doesn’t produce enough thyroid-stimulating hormone (TSH).
Q: What are other conditions associated with hypothyroidism?
Down’s syndrome
Turner’s syndrome
Coeliac disease
Q: What is the relationship between hypothyroidism and initial thyrotoxic phase?
Many causes of hypothyroidism may have an initial thyrotoxic phase, where there is excess thyroid hormone release before the gland becomes underactive.
Q: What are the general features of hypothyroidism?
Weight gain
Lethargy
Cold intolerance
Q: What are the skin features of hypothyroidism?
Dry (anhydrosis), cold, yellowish skin
Non-pitting oedema (e.g., hands, face)
Dry, coarse scalp hair
Loss of lateral aspect of eyebrows
Q: What are the gastrointestinal features of hypothyroidism?
Constipation
Q: What are the gynaecological features of hypothyroidism?
Menorrhagia (heavy menstrual bleeding)
Q: What are the neurological features of hypothyroidism?
Decreased deep tendon reflexes
Carpal tunnel syndrome
Q: What are some other features occasionally seen in hypothyroidism?
Hoarse voice
Q: What is the recommended initial starting dose of levothyroxine for elderly patients and those with ischemic heart disease?
Initial starting dose should be 25 mcg once daily, with dose titrated slowly.
For patients over 50 years or with severe hypothyroidism, the BNF recommends this approach.
Q: What is the initial starting dose of levothyroxine for patients without significant cardiac disease or severe hypothyroidism?
The initial starting dose should be 50-100 mcg once daily.
Q: After changing the levothyroxine dose, when should thyroid function tests be checked?
Thyroid function tests should be checked 8-12 weeks after a change in dose.
Q: What is the therapeutic goal for levothyroxine therapy in hypothyroidism?
The therapeutic goal is normalization of the thyroid-stimulating hormone (TSH) level.
Preferably aim for a TSH level in the range of 0.5-2.5 mU/L.
Q: How should levothyroxine doses be adjusted in pregnant women with hypothyroidism?
The dose should be increased by 25-50 mcg during pregnancy due to increased demands.
The TSH should be monitored carefully, aiming for a low-normal value.
Q: What are the side effects of levothyroxine therapy?
Hyperthyroidism (due to over-treatment)
Reduced bone mineral density
Worsening of angina
Atrial fibrillation
Q: Which substances reduce the absorption of levothyroxine?
Iron and calcium carbonate reduce the absorption of levothyroxine.
They should be taken at least 4 hours apart from levothyroxine.
Q: What is the structure of insulin?
Insulin is composed of 51 amino acids with a molecular weight of 5808 Da.
It consists of a dimer of an A-chain and a B-chain, linked by disulfide bonds.
Q: Where is insulin produced in the body?
Insulin is produced by the beta cells of the pancreas.
Q: What is the process of insulin synthesis?
Pro-insulin is formed in the rough endoplasmic reticulum of pancreatic beta cells.
Pro-insulin is cleaved to form insulin and C-peptide.
Insulin is stored in secretory granules and released in response to Ca2+.
Q: What is the function of insulin?
Secreted in response to hyperglycaemia.
Promotes glucose utilisation and glycogen synthesis in liver and muscles.
Inhibits lipolysis (fat breakdown).
Reduces muscle protein loss.
Increases cellular uptake of potassium via the Na+/K+ ATPase pump.
Q: How does insulin affect potassium in the body?
Insulin increases the cellular uptake of potassium by stimulating the Na+/K+ ATPase pump, which helps maintain potassium balance.
Q: What is the purpose of the insulin stress test?
The insulin stress test is used to investigate hypopituitarism.
Q: How is the insulin stress test performed?
IV insulin is administered.
Growth hormone (GH) and cortisol levels are then measured.
With normal pituitary function, both GH and cortisol should rise in response to the insulin administration.
Q: What is the expected response in a normal pituitary during the insulin stress test?
In a normal pituitary, both GH and cortisol should rise following the administration of IV insulin.
Q: What are the contraindications for the insulin stress test?
Epilepsy
Ischaemic heart disease
Adrenal insufficiency
Q: What are the signs of hypoglycaemia in patients receiving insulin therapy?
Sweating
Anxiety
Blurred vision
Confusion
Aggression
Q: What should a conscious patient with hypoglycaemia do?
Take 10-20g of a short-acting carbohydrate, such as:
A glass of Lucozade or any non-diet drink
Three or more glucose tablets
Glucose gel
Q: What should patients with insulin therapy have for emergencies where they cannot orally ingest carbohydrates?
Glucagon kit for emergency use, to raise blood glucose in unconscious patients or those unable to ingest oral glucose.
Q: What is reduced awareness of hypoglycaemia, and how can it be managed?
Frequent hypoglycaemic episodes may lead to reduced awareness of symptoms.
To restore awareness, allow glycaemic control to slip for a period of time.
Beta-blockers can also reduce hypoglycaemic awareness.
Q: What is lipodystrophy, and how can it affect insulin absorption?
Lipodystrophy presents as atrophy or lumps of subcutaneous fat at the injection sites.
It can be prevented by rotating injection sites.
If untreated, it can lead to erratic insulin absorption.
Q: What is an insulinoma?
A neuroendocrine tumour mainly arising from pancreatic Islets of Langerhans cells.
It is the most common pancreatic endocrine tumour.
Q: What is the association between multiple insulinomas and MEN-1?
50% of patients with multiple insulinomas have MEN-1 (Multiple Endocrine Neoplasia type 1).
Q: What are the typical features of hypoglycaemia in insulinoma?
Symptoms often occur early in the morning or just before meals, such as:
Diplopia
Weakness
Other signs of hypoglycaemia.
Q: What laboratory findings are indicative of an insulinoma?
High insulin levels
Raised proinsulin:insulin ratio
High C-peptide levels.
Q: How is insulinoma diagnosed?
Supervised, prolonged fasting (up to 72 hours) to provoke hypoglycaemia and assess insulin response.
CT scan of the pancreas.
Q: What is the treatment for insulinoma?
Surgery (if feasible).
If surgery is not possible, diazoxide and somatostatin can be used.
Q: What is Kallmann’s syndrome?
A cause of delayed puberty secondary to hypogonadotropic hypogonadism.
Usually inherited as an X-linked recessive trait.
It is caused by the failure of GnRH-secreting neurons to migrate to the hypothalamus.
Q: What is a key clinical clue in the diagnosis of Kallmann’s syndrome?
Anosmia (lack of smell) in a boy with delayed puberty.
Q: What are the key features of Kallmann’s syndrome?
Delayed puberty
Hypogonadism and cryptorchidism
Anosmia
Low sex hormone levels
Inappropriately low/normal LH and FSH levels
Normal or above-average height
Cleft lip/palate and visual/hearing defects (in some patients).
Q: What is the management of Kallmann’s syndrome?
Testosterone supplementation to induce puberty and secondary sexual characteristics.
Gonadotrophin supplementation may be used to induce sperm production if fertility is desired later in life.
Q: What is the karyotype associated with Klinefelter’s syndrome?
47, XXY karyotype.
Q: What are the key features of Klinefelter’s syndrome?
Taller than average
Lack of secondary sexual characteristics
Small, firm testes
Infertility
Gynaecomastia (increased incidence of breast cancer)
Elevated gonadotrophin levels but low testosterone.
Q: How is Klinefelter’s syndrome diagnosed?
Diagnosis is made by karyotype (chromosomal analysis).
Q: What is the inheritance pattern of Liddle’s syndrome?
Autosomal dominant.
Q: What are the key features of Liddle’s syndrome?
Hypertension
Hypokalaemic alkalosis
Caused by disordered sodium channels in the distal tubules, leading to increased reabsorption of sodium.
Q: What is the treatment for Liddle’s syndrome?
Amiloride or triamterene.
Q: What is Maturity-Onset Diabetes of the Young (MODY)?
A form of monogenic diabetes characterized by autosomal dominant inheritance, typically onset before 25 years of age, and insulin secretion impairment without major defects in insulin action.
Q: What are the main clinical features of MODY?
Mild non-ketotic hyperglycemia
Normal weight, no signs of insulin resistance
No diabetic ketoacidosis, except under severe stress
May be discovered incidentally or during pregnancy.
Q: How is MODY diagnosed?
Suspected in individuals with persistent hyperglycemia before age 25, without typical features of Type 1 or Type 2 diabetes.
Diagnosis confirmed by genetic testing.
Q: How is MODY treated?
Treatment varies by genetic subtype:
MODY2 (GCK mutation): May not require treatment due to mild hyperglycemia.
MODY3 (HNF1A mutation): Typically responds well to low-dose sulfonylureas.
Insulin therapy may be needed, especially during pregnancy or if sulfonylureas are ineffective.
Q: What is Multiple Endocrine Neoplasia (MEN)?
MEN is an autosomal dominant disorder that involves the development of tumors or hyperplasia in multiple endocrine glands.
Q: What are the three main types of MEN?
MEN type I
MEN type IIa
MEN type IIb
Q: What are the features of MEN type I?
3 P’s:
Parathyroid hyperplasia (95%): leading to hyperparathyroidism
Pituitary tumors (70%)
Pancreatic tumors (50%): e.g., insulinoma, gastrinoma (causing recurrent peptic ulceration)
Also: adrenal tumors and thyroid involvement
MEN1 gene mutation
Most common presentation: hypercalcemia
Q: What are the features of MEN type IIa?
2 P’s:
Parathyroid hyperplasia (60%)
Phaeochromocytoma
Medullary thyroid cancer (70%)
RET oncogene mutation
Q: What are the features of MEN type IIb?
1 P:
Phaeochromocytoma
Marfanoid body habitus
Neuromas
Medullary thyroid cancer
RET oncogene mutation
Q: What is the common mutation associated with MEN types IIa and IIb?
RET oncogene
Q: What is myxoedema coma?
Myxoedema coma is a medical emergency caused by severe hypothyroidism, typically presenting with confusion and hypothermia.
Q: What are the key features of myxoedema coma?
Confusion
Hypothermia
Severe hypothyroidism symptoms.
Q: What is the treatment for myxoedema coma?
IV thyroid replacement
IV fluid
IV corticosteroids (until coexisting adrenal insufficiency is excluded)
Electrolyte imbalance correction
Rewarming (sometimes)
Q: What is neuroblastoma?
Neuroblastoma is one of the top five causes of cancer in children, accounting for around 7-8% of childhood malignancies.
It arises from neural crest tissue of the adrenal medulla (most common site) and sympathetic nervous system.
Q: What are the common features of neuroblastoma?
Abdominal mass
Pallor and weight loss
Bone pain, limp
Hepatomegaly
Paraplegia
Proptosis
Q: What are the investigations for neuroblastoma?
Raised urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
Calcification may be seen on abdominal X-ray
Biopsy
Q: How is BMI calculated?
BMI = weight (kg) / height (m)²
Q: What is the BMI classification for obesity?
Underweight: < 18.49 kg/m²
Normal: 18.5 - 25 kg/m²
Overweight: 25 - 30 kg/m²
Obese class 1: 30 - 35 kg/m²
Obese class 2: 35 - 40 kg/m²
Obese class 3: > 40 kg/m²
Q: What is the general management approach for obesity?
Conservative: Diet, exercise
Medical: Orlistat, liraglutide
Surgical
Q: What is Orlistat, and how does it work?
Orlistat is a pancreatic lipase inhibitor used to manage obesity.
Adverse effects: Faecal urgency, incontinence, flatulence.
Criteria for use:
BMI ≥ 28 kg/m² with associated risk factors, or
BMI ≥ 30 kg/m²
Continued weight loss (e.g., 5% at 3 months)
Typically used for < 1 year.
Q: What is Liraglutide, and how is it used in obesity management?
Liraglutide is a GLP-1 mimetic used in type 2 diabetes mellitus (T2DM) and obesity.
Administered as a once daily subcutaneous injection.
Weight loss noted in significant proportions of T2DM patients, leading to its use in obesity.
NICE criteria for use:
BMI ≥ 35 kg/m²
Prediabetic hyperglycaemia (e.g., HbA1c 42-47 mmol/mol)
Q: What is the hormone profile of primary hyperparathyroidism?
PTH: Elevated
Ca2+: Elevated
Phosphate: Low
Urine calcium: creatinine clearance ratio: > 0.01
Q: What are the clinical features of primary hyperparathyroidism?
May be asymptomatic if mild
Recurrent abdominal pain (pancreatitis, renal colic)
Changes to emotional or cognitive state
Q: What is the most common cause of primary hyperparathyroidism?
Solitary adenoma (80% of cases)
Multifocal disease (10-15%)
Parathyroid carcinoma (< 1%)
Q: What is the hormone profile of secondary hyperparathyroidism?
PTH: Elevated
Ca2+: Low or normal
Phosphate: Elevated
Vitamin D: Low
Q: What are the clinical features of secondary hyperparathyroidism?
May have few symptoms initially
Eventually, may develop bone disease, osteitis fibrosa cystica, and soft tissue calcifications
Q: What is the main cause of secondary hyperparathyroidism?
Parathyroid gland hyperplasia due to low calcium, often in chronic renal failure
Q: What is the hormone profile of tertiary hyperparathyroidism?
Ca2+: Normal or high
PTH: Elevated
Phosphate: Decreased or normal
Vitamin D: Normal or decreased
Alkaline phosphatase: Elevated
Q: What are the clinical features of tertiary hyperparathyroidism?
Metastatic calcification
Bone pain and/or fractures
Nephrolithiasis (kidney stones)
Pancreatitis
Q: What is the most common cause of tertiary hyperparathyroidism?
Ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, usually affecting all 4 glands
Q: What is the difference between primary hyperparathyroidism and benign familial hypocalciuric hypercalcaemia?
In benign familial hypocalciuric hypercalcaemia, the urine calcium: creatinine clearance ratio is < 0.01, unlike primary hyperparathyroidism, where it is > 0.01.
Diagnosis is made by genetic testing.
Q: What are the indications for surgery in primary hyperparathyroidism?
Serum calcium > 1mg/dL above normal
Hypercalciuria > 400mg/day
Creatinine clearance < 30%
Episode of life-threatening hypercalcaemia
Nephrolithiasis
Age < 50 years
Neuromuscular symptoms
Reduction in bone mineral density (T score < -2.5)
Q: What are the indications for surgery in secondary (renal) hyperparathyroidism?
Bone pain
Persistent pruritus
Soft tissue calcifications
Q: How is tertiary hyperparathyroidism managed after a kidney transplant?
Allow 12 months to elapse after transplant, as many cases resolve.
If an autonomously functioning parathyroid gland is identified, it should be excised.
If unable to identify the culprit gland, total parathyroidectomy with re-implantation of part of the gland may be required.
Q: What is phaeochromocytoma?
A rare catecholamine-secreting tumour.
10% are familial and may be associated with MEN type II, neurofibromatosis, and von Hippel-Lindau syndrome.
Q: What are the typical features of phaeochromocytoma?
Hypertension (around 90% of cases, may be sustained)
Headaches
Palpitations
Sweating
Anxiety
Q: What is the most sensitive test for diagnosing phaeochromocytoma?
24-hour urinary collection of metanephrines (sensitivity 97%)
This test has replaced 24-hour urinary collection of catecholamines (sensitivity 86%).
Q: What is the definitive treatment for phaeochromocytoma?
Surgery is the definitive management.
Q: What is the pre-surgical management for phaeochromocytoma?
Alpha-blocker (e.g., phenoxybenzamine) should be given before a beta-blocker (e.g., propranolol) to stabilize the patient before surgery.
Q: What is a pituitary adenoma?
A benign tumour of the pituitary gland.
Common (10% of all people), but often asymptomatic or found incidentally.
Accounts for around 10% of adult brain tumours.
Q: How are pituitary adenomas classified?
Size:
Microadenoma: <1 cm
Macroadenoma: ≥1 cm
Hormonal status:
Secretory/functioning adenoma: Excess hormone production.
Non-secretory/functioning adenoma: No excess hormone production.
Q: What are the most common types of pituitary adenomas?
Prolactinomas: Most common, producing excess prolactin.
Non-secretory adenomas: Next most common.
GH-secreting adenomas: Produce excess growth hormone.
ACTH-secreting adenomas: Produce excess ACTH (Cushing’s disease).
Q: How do pituitary adenomas typically cause symptoms?
Excess hormones (e.g., Cushing’s disease, acromegaly, amenorrhea/galactorrhea).
Depletion of hormones (due to compression of normal pituitary tissue).
Non-functioning tumours: Present with generalised hypopituitarism.
Dural stretching: Causes headaches.
Optic chiasm compression: Causes bitemporal hemianopia.
Q: What is included in the investigation of a pituitary adenoma?
Pituitary blood profile (GH, prolactin, ACTH, FSH, LSH, TFTs).
Formal visual field testing.
MRI brain with contrast.
Q: What are the differential diagnoses for pituitary adenomas?
Pituitary hyperplasia
Craniopharyngioma
Meningioma
Brain metastases
Lymphoma
Hypophysitis
Vascular malformation (e.g., aneurysm)
Q: What are the treatment options for pituitary adenomas?
Medical therapy:
Prolactinomas: Treated with dopamine agonists (e.g., cabergoline, bromocriptine).
GH-secreting adenomas: Treated with somatostatin analogues (e.g., octreotide, lanreotide) and GH receptor antagonists (e.g., pegvisomant).
ACTH-secreting adenomas: Treated with cortisol synthesis inhibitors (e.g., ketoconazole, metyrapone) and neuromodulators (e.g., pasireotide).
Surgery:
Transsphenoidal surgery is the primary treatment, especially for non-functioning adenomas, and ACTH- or GH-secreting adenomas.
Surgery aims to remove the tumour, normalize hormone levels, and address compressive symptoms (e.g., visual problems).
Radiotherapy:
Indicated for residual or recurrent tumours post-surgery.
Q: What is the recommended management for prediabetes?
Lifestyle modification:
Weight loss, increased exercise, and diet changes.
Yearly follow-up with blood tests.
NICE recommendations:
Metformin for adults at high risk if blood glucose levels (fasting plasma glucose or HbA1c) show continued progression toward type 2 diabetes, despite intensive lifestyle changes.
Q: What are the two main types of impaired glucose regulation (IGR)?
Impaired Fasting Glucose (IFG): Due to hepatic insulin resistance.
Impaired Glucose Tolerance (IGT): Due to muscle insulin resistance.
IGT is more likely to progress to type 2 diabetes (T2DM) and cardiovascular disease than IFG.
Q: What are the definitions for IFG and IGT?
Impaired Fasting Glucose (IFG):
Fasting glucose ≥ 6.1 mmol/l but < 7.0 mmol/l.
Impaired Glucose Tolerance (IGT):
Fasting plasma glucose < 7.0 mmol/l and OGTT 2-hour value ≥ 7.8 mmol/l but < 11.1 mmol/l.
IGT is diagnosed after an oral glucose tolerance test (OGTT). A result between 7.8 mmol/l and 11.1 mmol/l indicates IGT (not diabetes).
Q: How does pregnancy affect thyroid function?
Increased thyroxine-binding globulin (TBG) levels in pregnancy cause an increase in total thyroxine levels.
This increase in total thyroxine does not affect free thyroxine levels
Q: What are the risks of untreated thyrotoxicosis in pregnancy?
Fetal loss
Maternal heart failure
Premature labour
Q: What is the most common cause of thyrotoxicosis in pregnancy?
Graves’ disease is the most common cause.
Transient gestational hyperthyroidism can also occur due to HCG activation of the TSH receptor.
Q: What is the preferred treatment for thyrotoxicosis during pregnancy?
Propylthiouracil (PTU) is traditionally used in the first trimester.
PTU is preferred over carbimazole, which is associated with an increased risk of congenital abnormalities.
Propylthiouracil is associated with an increased risk of severe hepatic injury, so careful monitoring is needed.
Q: What are the goals of managing thyrotoxicosis in pregnancy?
Keep maternal free thyroxine levels in the upper third of the normal reference range to avoid fetal hypothyroidism.
Thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation to assess the risk of neonatal thyroid problems.
Block-and-replace regimes should not be used during pregnancy.
Radioiodine therapy is contraindicated in pregnancy.
Q: What is the management for hypothyroidism during pregnancy?
Thyroxine is safe during pregnancy.
Serum thyroid-stimulating hormone (TSH) should be measured in each trimester and 6-8 weeks postpartum.
Women often need an increased dose of thyroxine (up to 50% more) starting as early as 4-6 weeks of pregnancy.
Breastfeeding is safe while on thyroxine.
Q: What are the two most common causes of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia (60-70% of cases)
Adrenal adenoma (20-30% of cases)
Other causes include unilateral hyperplasia, familial hyperaldosteronism, and adrenal carcinoma.
Q: What are the common features of primary hyperaldosteronism?
Hypertension (often treatment-resistant)
Hypokalaemia (e.g., muscle weakness, though this occurs in only 10-40% of cases)
Metabolic alkalosis
Muscle weakness is more common with adrenal adenomas.
Q: What is the first-line investigation for primary hyperaldosteronism?
Plasma aldosterone/renin ratio
High aldosterone with low renin levels (due to negative feedback from sodium retention) suggests primary hyperaldosteronism.
Q: What investigations are used to differentiate between the causes of primary hyperaldosteronism?
High-resolution CT abdomen: Identifies adrenal abnormalities.
Adrenal vein sampling (AVS): Differentiates between unilateral adenoma and bilateral hyperplasia if CT is normal.
Q: What is the management for primary hyperaldosteronism?
Adrenal adenoma: Surgery (laparoscopic adrenalectomy).
Bilateral adrenocortical hyperplasia: Aldosterone antagonists (e.g., spironolactone).
Q: What is the most common cause of primary hyperparathyroidism?
85% of cases are caused by a solitary parathyroid adenoma.
Q: What mnemonic can help remember the symptoms of primary hyperparathyroidism?
“Bones, stones, abdominal groans, and psychic moans”
Bones: Bone pain/fractures (osteitis fibrosa cystica)
Stones: Renal stones
Abdominal groans: Anorexia, nausea, constipation, peptic ulceration, pancreatitis
Psychic moans: Depression, confusion
Other symptoms: Polydipsia, polyuria, hypertension
Q: What are the main investigations for primary hyperparathyroidism?
Blood tests:
Raised calcium
Low phosphate
PTH: May be raised or normal (inappropriately, given raised calcium)
Technetium-MIBI subtraction scan
X-ray findings:
Pepperpot skull (due to cortical bone thinning)
Osteitis fibrosa cystica
Q: What is the definitive treatment for primary hyperparathyroidism?
Total parathyroidectomy.
Q: When might conservative management be considered for primary hyperparathyroidism?
If calcium is less than 0.25 mmol/L above the upper limit of normal, the patient is >50 years old, and there is no evidence of end-organ damage.
Q: What is the role of cinacalcet in the treatment of primary hyperparathyroidism?
Cinacalcet is a calcimimetic that mimics calcium’s action on tissues, activating the calcium-sensing receptor. It may be used for patients not suitable for surgery.
Q: Where is prolactin produced?
Anterior pituitary
Q: What are the main functions of prolactin?
Stimulates breast development (initially and further hyperplasia during pregnancy)
Stimulates milk production
Decreases GnRH pulsatility at the hypothalamic level
Blocks the action of LH on the ovary or testis to a lesser extent.
Q: What factors increase prolactin secretion?
Thyrotropin-releasing hormone (TRH)
Pregnancy
Oestrogen
Breastfeeding
Sleep
Stress
Drugs: e.g., metoclopramide, antipsychotics
Q: What factors decrease prolactin secretion?
Dopamine
Dopaminergic agonists
Q: What is the primary inhibitory factor for prolactin release?
Dopamine
Dopamine agonists (e.g., bromocriptine) can be used to control galactorrhoea.
Q: What are the features of excess prolactin in men and women?
Men: Impotence, loss of libido, galactorrhoea
Women: Amenorrhoea, galactorrhoea
Q: What are common causes of raised prolactin?
Prolactinoma
Pregnancy
Oestrogens
Physiological: Stress, exercise, sleep
Acromegaly (1/3 of patients)
Polycystic ovarian syndrome
Primary hypothyroidism (due to TRH stimulating prolactin release)
Q: What are some drug causes of raised prolactin?
Metoclopramide, domperidone
Phenothiazines
Haloperidol
Very rare: SSRIs, opioids
Q: What is a prolactinoma?
A prolactinoma is a type of pituitary adenoma (benign tumour) that produces an excess of prolactin.
Q: What are the features of prolactinomas in women?
Amenorrhoea
Infertility
Galactorrhoea
Osteoporosis
Q: What are the features of prolactinomas in men?
Impotence
Loss of libido
Galactorrhoea
Q: What additional symptoms may be seen with macroadenomas?
Headache
Visual disturbances: Bitemporal hemianopia (lateral visual fields) or upper temporal quadrantanopia
Symptoms of hypopituitarism
Q: What is the diagnosis for a prolactinoma?
MRI is used to diagnose a prolactinoma.
Q: How are prolactinomas managed?
Medical treatment: Dopamine agonists (e.g., cabergoline, bromocriptine) to inhibit prolactin release
Surgery: If the patient cannot tolerate or fails to respond to medical therapy, trans-sphenoidal surgery is typically performed (unless there is significant extra-pituitary extension).
Q: What is parathyroid hormone (PTH)?
PTH is a polypeptide hormone secreted from the parathyroid glands.
It plays a vital role in calcium homeostasis by maintaining blood calcium levels within a narrow range.
Q: How is calcium regulated in the body?
Calcium enters the body through the intestines and exits through urine and faeces.
The main calcium reservoir is the bone.
In the blood, calcium exists in three forms:
Free calcium (physiologically active)
Calcium bound to albumin
Calcium complexed with anions
Q: What is the structure and function of PTH?
PTH is a single-chain polypeptide containing 84 amino acids.
It is secreted by the chief cells of the parathyroid glands in response to low blood calcium levels.
Function:
In the bone: Increases osteoclast activity, causing bone resorption and releasing calcium and phosphate into the blood.
In the kidney:
Increases activation of vitamin D, which promotes calcium absorption.
Increases calcium reabsorption from the renal tubules and increases phosphate excretion.
Q: How does PTH regulate calcium levels?
Negative feedback loop:
Low calcium levels are detected by the parathyroid glands.
PTH is secreted into the blood, causing calcium release from bones and reabsorption in the kidneys.
Calcium levels rise and are detected by the parathyroid glands, which then reduce PTH secretion.
Q: What is Primary Hyperparathyroidism?
A condition where the parathyroid glands are overactive, leading to excessive secretion of PTH and resulting in hypercalcaemia.
Common causes include hyperplasia, adenomas, or malignancies.
Symptoms include renal calculi, constipation, polyuria, abdominal pain, and low mood.
Treatment: Surgical removal of the glands.
Q: What is PTH-related peptide (PTHrp)?
A polypeptide that has a similar structure to PTH and can be secreted by cancer cells (e.g., squamous cell bronchial carcinoma).
It causes hypercalcaemia but cannot activate vitamin D, unlike PTH.
Q: What is Riedel’s thyroiditis?
A rare cause of hypothyroidism.
Characterized by dense fibrous tissue replacing the normal thyroid parenchyma.
Q: What are the clinical features of Riedel’s thyroiditis?
Hard, fixed, painless goitre on examination.
Hypothyroidism symptoms (e.g., fatigue, weight gain, cold intolerance).
Q: What is Riedel’s thyroiditis associated with?
Retroperitoneal fibrosis (fibrous tissue growth in the retroperitoneal space).
Q: What is the mechanism of action of SGLT-2 inhibitors?
They reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule.
This reduces glucose reabsorption and increases urinary glucose excretion.
Q: What are the important adverse effects of SGLT-2 inhibitors?
Urinary and genital infections (due to glycosuria).
Fournier’s gangrene (rare but severe).
Normoglycaemic ketoacidosis.
Increased risk of lower-limb amputation (close monitoring of feet is needed).
Q: How do SGLT-2 inhibitors affect weight in patients with type 2 diabetes mellitus?
Weight loss is often seen, which can be beneficial for managing type 2 diabetes mellitus.
Q: What is Sick Euthyroid Syndrome (or Non-Thyroidal Illness)?
A condition where thyroid function tests are altered during systemic illness.
It is characterized by low levels of thyroxine (T4) and T3, but the TSH is often inappropriately normal (higher than expected given the low T4 and T3).
Q: What is the typical thyroid profile seen in Sick Euthyroid Syndrome?
TSH is often within the normal range, but may be inappropriately normal given low T4 and T3 levels.
T4 and T3 levels are typically low.
Q: Is treatment required for Sick Euthyroid Syndrome?
No treatment is usually required.
Changes in thyroid function are typically reversible upon recovery from the underlying systemic illness.
Q: What are the key endocrine and metabolic changes in the stress response to surgery?
Substrate mobilization
Muscle protein loss
Sodium and water retention
Suppression of anabolic hormones
Activation of the sympathetic nervous system
Immunological and hematological changes
Q: Which hormones increase during the stress response to surgery?
Growth hormone
Cortisol
Renin
ACTH
Aldosterone
Prolactin
Antidiuretic hormone
Glucagon
Q: Which hormones decrease during the stress response to surgery?
Insulin
Testosterone
Thyroid-stimulating hormone (TSH)
Luteinizing hormone (LH)
Follicle stimulating hormone (FSH)
Q: How does cortisol affect metabolism during the stress response?
Increases skeletal muscle protein breakdown
Stimulates lipolysis
Exhibits an anti-insulin effect
Has mineralocorticoid effects
Anti-inflammatory effects
Q: What effect does insulin have during surgery?
Insulin release is inhibited by stress, leading to insulin resistance.
Initially, there is functional insulin deficiency, contributing to hyperglycemia.
Q: What is the effect of surgery on thyroid hormones (T4 and T3)?
Decreased thyroid hormone production post-surgery, inversely correlated with sympathetic activity.
Recovery occurs within a few days after surgery.
Q: What is the effect of stress response on protein metabolism during surgery?
Initially, protein anabolism is inhibited, followed by enhanced catabolism in severe stress.
Skeletal muscle protein is mainly affected.
Amino acids released are used for gluconeogenesis.
Q: How does lipid metabolism change during surgery?
Increased catecholamine, cortisol, and glucagon secretion promotes lipolysis and ketone body production.
Q: What factors can modify the stress response?
Opioids suppress hormone secretion but may prolong recovery and increase ventilatory support needs.
Spinal anaesthesia reduces hormone and glucose changes but does not alter cytokine responses.
Nutrition (enteral feeding) improves recovery and mitigates adverse effects.
Growth hormone and anabolic steroids may improve outcomes.
Normothermia reduces the metabolic response.
Q: What is Subacute (De Quervain’s) Thyroiditis and what is its cause?
Subacute thyroiditis (also called De Quervain’s thyroiditis) is a condition believed to be triggered by a viral infection, often presenting with hyperthyroidism.
Q: What are the 4 phases of Subacute (De Quervain’s) Thyroiditis?
Phase 1 (3-6 weeks): Hyperthyroidism, painful goitre, elevated ESR (erythrocyte sedimentation rate).
Phase 2 (1-3 weeks): Euthyroid (normal thyroid function).
Phase 3 (weeks to months): Hypothyroidism.
Phase 4: Return to normal thyroid structure and function.
Q: What are the common investigations for Subacute (De Quervain’s) Thyroiditis?
Thyroid scintigraphy: Globally reduced uptake of iodine-131.
Q: How is Subacute (De Quervain’s) Thyroiditis managed?
Self-limiting: Most patients do not require treatment.
Pain relief: Aspirin or other NSAIDs may help with thyroid pain.
In severe cases, steroids may be used, especially if hypothyroidism develops.
Q: What is Subclinical Hyperthyroidism?
Subclinical hyperthyroidism is defined as:
Normal serum free thyroxine (T4) and triiodothyronine (T3) levels
A TSH (thyroid-stimulating hormone) level below the normal range (usually < 0.1 μU/L).
Q: What are the common causes of Subclinical Hyperthyroidism?
Multinodular goitre, especially in elderly females
Excessive thyroxine (e.g., from overuse of thyroid hormone replacement therapy) can cause a similar biochemical picture.
Q: Why is it important to recognize Subclinical Hyperthyroidism?
Cardiovascular risk: Increased risk of atrial fibrillation.
Bone health: May lead to osteoporosis.
Quality of life: Can impact quality of life and may increase the risk of dementia.
Q: What is the management approach for Subclinical Hyperthyroidism?
Observation: TSH levels often revert to normal on their own. Treatment is considered only if levels remain persistently low.
Therapeutic trial: A trial of low-dose antithyroid agents (e.g., methimazole) for 6 months may be considered to try and induce remission.
Q: What is Subclinical Hypothyroidism?
TSH is raised, but T3 and T4 are normal.
Patients often have no obvious symptoms.
Q: What are the risks associated with Subclinical Hypothyroidism?
Progression to overt hypothyroidism: Risk is 2-5% per year, higher in men.
Thyroid autoantibodies: Presence of these increases the risk of progression.
Q: How is Subclinical Hypothyroidism managed?
TSH > 10 mU/L with normal free thyroxine:
Consider offering levothyroxine if TSH is > 10 mU/L on 2 separate occasions 3 months apart.
TSH between 5.5 - 10 mU/L with normal free thyroxine:
< 65 years: Offer a 6-month trial of levothyroxine if TSH is in this range on 2 separate occasions and there are symptoms of hypothyroidism.
> 80 years: A ‘watch and wait’ strategy is often used. If asymptomatic, observe and repeat thyroid function in 6 months.
Q: How do Sulfonylureas work in managing Type 2 diabetes mellitus?
Sulfonylureas increase pancreatic insulin secretion.
Effective only if functional beta cells are present.
They bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells.
Q: What are the common adverse effects of Sulfonylureas?
Hypoglycaemic episodes (more common with long-acting preparations like chlorpropamide).
Weight gain.
Q: What are the rarer adverse effects of Sulfonylureas?
Hyponatraemia (due to syndrome of inappropriate ADH secretion).
Bone marrow suppression.
Hepatotoxicity (typically cholestatic).
Peripheral neuropathy.
Q: Are Sulfonylureas safe during pregnancy and breastfeeding?
Avoid use in pregnancy and breastfeeding.
Q: What class of drugs are Thiazolidinediones and what condition do they treat?
A: Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus.
Q: How do Thiazolidinediones work in the body?
A: They are agonists of the PPAR-gamma receptor and reduce peripheral insulin resistance.
Q: What are common adverse effects of Thiazolidinediones?
A: Weight gain and liver impairment (monitor LFTs).
Q: Why are Thiazolidinediones contraindicated in heart failure?
A: They cause fluid retention, and the risk is increased if the patient also takes insulin.
Q: Are features of hyperthyroidism or hypothyroidism commonly seen in patients with thyroid malignancies?
A: No, they are not commonly seen as thyroid malignancies rarely secrete thyroid hormones.
Q: What is the most common type of thyroid cancer and what is its prognosis?
A: Papillary thyroid cancer, accounting for 70% of cases, often in young females with an excellent prognosis.
Q: What percentage of thyroid cancers are follicular, and what are its characteristics?
A: 20%; it may appear macroscopically encapsulated, but microscopic capsular invasion is seen. Vascular invasion predominates.
Q: What is unique about medullary thyroid carcinoma?
A: It is a cancer of parafollicular (C) cells, secretes calcitonin, and is part of MEN-2 syndrome.
Q: What percentage of thyroid cancers is anaplastic, and what are its treatment options?
A: 1%; it is not responsive to treatment and can cause pressure symptoms. Treatment is resection where possible, with palliation through isthmusectomy and radiotherapy.
Q: What type of thyroid cancer is associated with Hashimoto’s thyroiditis?
A: Lymphoma, which is rare.
Q: What is the management for papillary and follicular thyroid cancer?
A: Total thyroidectomy followed by radioiodine (I-131) to kill residual cells, with yearly thyroglobulin levels to detect early recurrent disease.
Q: What is the most common type of thyroid cancer in elderly females, and what are its common features?
A: Anaplastic carcinoma, with local invasion being a common feature.
Q: What percentage of patients with Graves’ disease are affected by thyroid eye disease?
A: 25-50%
Q: What is the proposed pathophysiology of thyroid eye disease?
A: It is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor, leading to retro-orbital inflammation and resulting in glycosaminoglycan and collagen deposition in the muscles.
Q: What is the most important modifiable risk factor for the development of thyroid eye disease?
A: Smoking
Q: How can radioiodine treatment affect thyroid eye disease, and what can help reduce this risk?
A: Radioiodine treatment may increase inflammatory symptoms, with around 15% of patients with Graves’ disease developing or having worsening of eye disease. Prednisolone may help reduce the risk.
Q: List some common features of thyroid eye disease.
A: Exophthalmos, conjunctival oedema, optic disc swelling, ophthalmoplegia, and inability to close the eyelids which may lead to sore, dry eyes and risk of exposure keratopathy.
Q: What are the management options for thyroid eye disease?
A: Smoking cessation, topical lubricants, steroids, radiotherapy, and surgery.
Q: What is exposure keratopathy and how is it caused by thyroid eye disease?
A: Exposure keratopathy is caused by eyelid retraction and proptosis (exophthalmos) leading to corneal exposure, dryness, irritation, and corneal ulceration.
Q: What are the symptoms of exposure keratopathy?
A: Foreign body sensation, pain, photophobia, and in severe cases, corneal scarring and vision impairment.
Q: What is optic neuropathy and what are its signs?
A: Optic neuropathy is a serious complication of thyroid eye disease where enlarged extraocular muscles compress the optic nerve, leading to reduced visual acuity, color vision deficits, and visual field defects.
Q: What are strabismus and diplopia in the context of thyroid eye disease?
A: Fibrosis and enlargement of extraocular muscles can result in restrictive strabismus, causing misalignment of the eyes and double vision (diplopia), affecting visual function and quality of life.
Q: What are the urgent symptoms/signs indicating the need for ophthalmologist review in patients with established thyroid eye disease according to EUGOGO guidelines?
A: Unexplained deterioration in vision, change in color vision quality, eye ‘popping out’ (globe subluxation), obvious corneal opacity, cornea visible when eyelids are closed, and disc swelling.
Q: What thyroid function results are typically seen in thyrotoxicosis, such as Graves’ disease?
A: TSH: Low, Free T4: High. In T3 thyrotoxicosis, the free T4 will be normal.
Q: What thyroid function results are typical of primary hypothyroidism (e.g., primary atrophic hypothyroidism)?
A: TSH: High, Free T4: Low.
Q: What thyroid function results are seen in secondary hypothyroidism?
A: TSH: Low, Free T4: Low. Replacement steroid therapy is required before thyroxine.
Q: What thyroid function results are seen in sick euthyroid syndrome (non-thyroidal illness)?
A: TSH: Low (sometimes normal), Free T4: Low. T3 is particularly low in these patients. This is common in hospital inpatients.
Q: What thyroid function results are seen in subclinical hypothyroidism?
A: TSH: High, Free T4: Normal.
Q: What thyroid function results are typically seen in poor compliance with thyroxine?
A: TSH: High, Free T4: Normal.
Q: What thyroid function results are seen with steroid therapy?
A: TSH: Low, Free T4: Normal.
Q: What is the primary aim of investigating thyroid nodules?
A: The primary aim is to exclude thyroid cancer, which accounts for around 5% of all nodules depending on the patient demographic.
Q: What are the common benign causes of thyroid nodules?
A: Multinodular goitre, thyroid adenoma, Hashimoto’s thyroiditis, cysts (colloid, simple, or hemorrhagic).
Q: What are the common malignant causes of thyroid nodules?
A: Papillary carcinoma (most common malignant cause), follicular carcinoma, medullary carcinoma, anaplastic carcinoma, lymphoma.
Q: What investigation should be performed in all patients with thyroid nodules?
A: Thyroid function tests should be checked in all patients.
Q: What is the first-line imaging technique for investigating thyroid nodules?
A: Ultrasonography is the first-line imaging of choice, which may help determine if the nodule has features suspicious of malignancy.
Q: What is thyroid storm?
A: Thyroid storm is a rare but life-threatening complication of thyrotoxicosis, typically seen in patients with established thyrotoxicosis, and is rarely seen as the presenting feature.
Q: What are some common precipitating events for thyroid storm?
A: Thyroid or non-thyroidal surgery, trauma, infection, acute iodine load (e.g., CT contrast media).
Q: What are the clinical features of thyroid storm?
A: Fever >38.5ºC, tachycardia, confusion and agitation, nausea and vomiting, hypertension, heart failure, abnormal liver function tests (jaundice).
Q: What is the symptomatic treatment for thyroid storm?
A: Paracetamol (for fever) and treatment of the underlying precipitating event.
Q: What are the key treatments for thyroid storm?
A: Beta-blockers (typically IV propranolol), anti-thyroid drugs (e.g., methimazole or propylthiouracil), Lugol’s iodine, and dexamethasone (blocks the conversion of T4 to T3).
Q: How does dexamethasone help in the treatment of thyroid storm?
A: Dexamethasone blocks the conversion of T4 to T3.
Q: What is the most common cause of thyrotoxicosis?
A: Graves’ disease, accounting for around 50-60% of cases.
Q: What are some common causes of thyrotoxicosis?
A: Graves’ disease, toxic nodular goitre, acute phase of subacute (de Quervain’s) thyroiditis, acute phase of post-partum thyroiditis, acute phase of Hashimoto’s thyroiditis, amiodarone therapy, and contrast use.
Q: How does amiodarone therapy contribute to thyrotoxicosis?
A: Amiodarone can cause thyrotoxicosis, particularly in elderly patients with pre-existing thyroid disease (e.g., multinodular goitre, Graves’). It can cause hyperthyroidism due to a large iodine load on the thyroid.
Q: What are the typical thyroid function test results in thyrotoxicosis?
A: TSH is low, and T4 and T3 are elevated.
Q: What investigations are done in thyrotoxicosis?
A: Thyroid function tests (TSH, T4, T3), thyroid autoantibodies, and isotope scanning if needed. Other investigations are not routinely done.
Q: What are some general features of thyrotoxicosis?
A: Weight loss, ‘manic’ behavior, and restlessness, as well as heat intolerance.
Q: What cardiac symptoms can be seen in thyrotoxicosis?
A: Palpitations, tachycardia, and high-output cardiac failure, which may occur in elderly patients. A reversible cardiomyopathy can rarely develop.
Q: What skin features are associated with thyrotoxicosis?
A: Increased sweating, pretibial myxoedema (erythematous, oedematous lesions above the lateral malleoli), and thyroid acropachy (clubbing).
Q: What gastrointestinal symptoms can occur in thyrotoxicosis?
A: Diarrhoea.
Q: What gynaecological feature is commonly seen in women with thyrotoxicosis?
A: Oligomenorrhea.
Q: What neurological features are associated with thyrotoxicosis?
A: Anxiety and tremor.
Q: What is toxic multinodular goitre?
A: Toxic multinodular goitre is a condition where a thyroid gland contains several autonomously functioning thyroid nodules, leading to hyperthyroidism.
Q: What does nuclear scintigraphy reveal in toxic multinodular goitre?
A: Patchy uptake.
Q: What is the treatment of choice for toxic multinodular goitre?
A: Radioiodine therapy.
Q: What is the purpose of the water deprivation test?
A: The water deprivation test is used to evaluate patients with polydipsia.
Q: How is the water deprivation test performed?
A: The patient is prevented from drinking water, asked to empty their bladder, and urine and plasma osmolalities are measured hourly.
Q: What are the results of the water deprivation test for a normal patient?
A: Starting plasma osmolality: Normal, Final urine osmolality: >600, Urine osmolality post-DDAVP: >600.
Q: What are the results of the water deprivation test for psychogenic polydipsia?
A: Starting plasma osmolality: Low, Final urine osmolality: >400, Urine osmolality post-DDAVP: >400.
Q: What are the results of the water deprivation test for cranial diabetes insipidus (DI)?
A: Starting plasma osmolality: High, Final urine osmolality: <300, Urine osmolality post-DDAVP: >600.
Q: What are the results of the water deprivation test for nephrogenic diabetes insipidus (DI)?
A: Starting plasma osmolality: High, Final urine osmolality: <300, Urine osmolality post-DDAVP: <300.
In DKA, if the ketonaemia and acidosis have not been resolved within 24 hours, what do you do
review by senior
In diabetes, if someone has an egfr of <30, what cant you give
metformin
What type of drug is gliclazide
sulfonylurea
What type of drug is pioglitazone
thiazolidinediones
What type of drug is liraglutide
GLP 1 mimetic
What should you do when orlistat isnt enough
add liraglutide
How are GLP 1 agonists given
injection
How do you confirm acromegaly after raised igf1
OGTT + serial GH measurements
What effect on the pituitary can haemochromatosis have
hypogonadotrophic hypogonadism
How would you test diabetic neuropathy in the feet
Test sensation using a 10 g monofilament
What can be given as treatment for turners
GH
What effect do steroids have on WBCs
reduce but neutrophils increase
What are typical values for tertiary hyperparathyroidism
PTH super high, moderately raised calcium
In DKA management, if blood glucose is <14, what should you do
an infusion of 10% dextrose should be started at 125 mls/hr in addition to the saline regime
How do you treat MODY
sulfonylurea
causes of raised prolactin
Causes of raised prolactin - the p’s
pregnancy
prolactinoma
physiological
polycystic ovarian syndrome
primary hypothyroidism
phenothiazines, metoclopramide, domperidone
Visual defect caused by prolactinoma or other pituitary adenoma
Bi temporal superior quadrantanopia into bitemporal hemianopia
Visual defect caused by craniopharyngioma
Bi temporal inferior quadrantanopia into bitemporal hemianopia
Causes of hypoglycaemia pneumonic
EXPLAIN
Exogenous drugs (typically sulfonylureas or insulin)
Pituitary insufficiency
Liver failure
Addison’s disease
Islet cell tumours (insulinomas)
Non-pancreatic neoplasms
whipples triad for insulinoma
1) hypoglycaemia with fasting or exercise, 2) reversal of symptoms with glucose, and 3) recorded low BMs at the time of symptoms is hallmark for an insulinoma
When would you give metformin for T1DM
BMI>25
What does an unrecordable blood glucose measurement mean
super high glucose rather than super low
Hypothyroidism vs hyperthyroidism symptoms
Not sure if this will help anyone but one of the consultants in the hospital described hyperthyroidism as everything going up besides weight and periods (i.e. heart rate, diarrhoea etc.) and hypothyroidism as everything going down besides weight and periods
What is the most common cause of secondary hypertension
primary hyperaldosteronism
hypothyroidism but with headache worse at night, reduced GNRH etc cause
pituitary adenoma (non functioning)
when taking medications for addisons, how should they be taken
Split with the majority in the first half of the day
what is the difference between secondary and tertiary hypothyroidism
secondary - pituitary
tertiary - hypothalamic
