Endocrine and Metabolic Flashcards
What is Addison’s Disease?
Autoimmune destruction of adrenal glands (primary hypoadrenalism) which leads to reduced cortisol and aldosterone
What are the symptoms and key diagnostic factors of Addison’s Disease?
- Fatigue
- Anorexia
- Weight loss
- Hyperpigmentation
- Acute adrenal crisis = hypotension and tachycardia leading to collapse
- Salt craving
- Muscle weakness
- N + V
- Postural hypotension
- Axillary + Pubic hair loss in women
What is the NICE guidelines investigation for Addison’s?
- 9am serum cortisol
- > 500 nmol/L = unlikely
- > 100-500 nmol/L = ACTH stimulation test or repeat test
- ACTH stimulation test (short SynACTHen test)
- Serum electrolytes for hyponatremia and hyperkalaemia
- Serum aldosterone (suppressed)
What is the NICE guidelines management for Addison’s?
Glucocorticoid = Hydrocortisone total daily dose 15 mg to 25 mg orally in 2 to 4 divided doses.
Mineralocorticoid = Fludrocortisone total daily dose initially 50 micrograms and adjusted according to response up to 300 micrograms orally. Consider a higher daily dose orally for young and physically active people.
If under physical or psychological stress, apply sick day rules (double dose of corticosteroid to mimic usual increase during stress)
What is Cushing’s Syndrome?
Cushing’s syndrome is a collection of symptoms that develop as the result of very high levels of cortisol in the body.
What are the ACTH dependent causes of Cushing’s?
- Cushing’s Disease (80%) : pituitary tumour secreting ACTH producing adrenal hyperplasia
- Ectopic ACTH production (5-10%) : e.g. small cell lung cancer is the most common cause of
What are the ACTH independent causes of Cushing’s?
- Iatrogenic : steroids
- Adrenal adenoma (5-10%)
- Adrenal carcinoma
- Carney complex : syndrome including cardiac myxoma
- Micronodular adrenal dysplasia (very rare)
What is Pseudo-Cushing’s?
Mimics Cushing’s, often due to alcohol excess or severe depression.
Causes false positive dexamethasone suppression test or 24h urinary free cortisol
Insulin stress test may be used to differentiate
Symptoms and key diagnostic factors of Cushing’s
- Facial plethora
- Supraclavicular fullness
- Violaceous Striae + easy bruising
- Menstrual irregularities
- Linear growth deceleration in children
- Hypertension
- DM
- Premature osteoporosis
- Weight gain + central obesity
- Acne
- Low libido
Investigations for Cushing’s
- Overnight 1mg dexamethasone suppression test : morning cortisol is not suppressed
- 24h urinary free cortisol (unless kidney failure)
- If ACTH is suppressed night = likely non-ACTH dependent
- High dose dexamethasone suppression test
- Cortisol unsuppressed and ACTH suppressed = non ACTH
- Cortisol suppressed and ACTH suppressed = Cushing’s Disease
- Cortisol and ACTH unsuppressed = Ectopic ACTH
What are other investigations to consider for Cushing’s?
- Serum Glucose
- ABG for hypokalaemic metabolic alkalosis
- Pituitary MRI if ACTH dependent
- Adrenal CT if ACTH independent
- Insulin stress test to differentiate with pseudo-Cushing’s
Management for Cushing’s
Cushing’s disease - Transsphenoidal pituitary adenomectomy
Ectopic ACTH or CRH syndrome - Surgical resection or ablation of tumour + metastasis
Unilateral adrenal carcinoma or adenoma - unilateral adrenalectomy or resection
Bilateral adrenal hyperplasia or adenoma - Bilateral adrenalectomy + corticosteroid replacement therapy
What is Hypothyroidism and the types?
Conditions that result in low thyroxine levels in the body.
Primary - there is a problem with the gland itself
Secondary - there is a problem outside the thyroid gland, usually the pituitary gland
Congenital - due to a problem with the thyroid dysgenesis or thyroid dyshormonogenesis
What are the causes of primary Hypothyroidism?
Hashimoto’s Thyroiditis: An autoimmune condition and MC in developed countries. It involves immune-mediated destruction of thyroid tissue, increases risk of MALT lymphoma
Subacute (De Quervain’s) Thyroiditis: Often follows a viral infection, leads to temporary thyroid inflammation and initial hyperthyroidism, followed by hypothyroidism.
Riedel Thyroiditis: A rare form of thyroiditis where fibrous tissue replaces thyroid tissue, potentially leading to primary hypothyroidism.
Postpartum Thyroiditis: An autoimmune inflammation that occurs within a year after childbirth, sometimes resulting in temporary hypothyroidism.
Drug-Induced Hypothyroidism: Medications like lithium and amiodarone can interfere with thyroid hormone synthesis or release, leading to primary hypothyroidism.
Iodine Deficiency: Inadequate iodine intake impairs thyroid hormone synthesis, causing primary hypothyroidism. It is a common cause in areas with low dietary iodine
What are causes of secondary Hypothyroidism?
Pituitary Tumors: Tumors in the pituitary gland can impair TSH production, leading to reduced thyroid function. Adenomas are the most common type of benign tumor affecting pituitary function
Hypothalamic Dysfunction: Lesions, trauma, or diseases decrease the release of thyrotropin-releasing hormone (TRH), reducing TSH production
Pituitary Surgery or Radiation: Treatment for pituitary tumors or other brain conditions may damage pituitary tissue
Sheehan’s Syndrome: Occurs after significant postpartum hemorrhage, leading to pituitary infarction and decreased TSH production due to pituitary damage
H&E for Hypothyroidism
- Weight gain
- Lethargy
- Cold intolerance
- Dry, cold, yellowish skin
- Non-pitting oedema
- Dry, coarse hair
- Constipation
- Menorrhagia
- Decreased deep tendon reflexes
- Carpal tunnel syndrome
Investigations for Hypothyroidism
TFT’s
Primary - high TSH, low T4
Secondary - low TSH, low T4
Thyroid Autoantibodies
Anti-thyroid peroxidase (anti-TPO) for Hashimoto’s
Iodine Scan
Global reduced uptake - De Quervain’s (Subacute)
Dosing + Changes depending on patients + Monitoring
Management of Hypothyroidism
Levothyroxine 50-100mcg OD
- reduce starting dose for patients with cardiac disease, severe hypothyroidism or patients > 50
- increase starting dose in pregnant women
- TFTs after 8-12 weeks
What are the side effects of levothyroxine?
- Hyperthyroidism
- Reduced bone mineral density
- Worsening of angina
- Atrial fibrillation
- Interactions with iron and calcium carbonate as it causes reduced absorption of levothyroxine so give 4 hours apart
What is Diabetic Ketoacidosis?
- Associated with T1DM
- Absolute lack of insulin - lack of glucose uptake - breakdown of fats for energy use - ketone production
What is the Triad for Diabetic Ketoacidosis?
Hyperglycaemia
Ketonaemia
Metabolic Acidosis
What is Diabetic Ketoacidosis caused by?
- Infection/ Acute illness
- Non-adherence to insulin regime and diabetes medication
H&E for Diabetic Ketoacidosis
- N+V
- Dehydration
- Polyuria and polydipsia
- Hyperventilation (Kussmaul Breathing)
- Abdo Pain
- Ketonic Breath (sweet almond smell)
- Collapse/ confusion
Investigations for Diabetic Ketoacidosis
- Ketones > 3 mmol/L
- pH < 7.3 (high anion gap)
- Plasma glucose > 11
Management of Diabetic Ketoacidosis
- Saline + Potassium Chloride (if K+ < 5.5)
- IV Insulin (0.1 unit/kg/hour) after fluids, only when K+ is not <3.5
- Include 10% Dextrose in fluid once glucose falls < 14 mmol/L
- Continue long acting insulin, stop short-acting insulin
- Treat underlying cause, e.g. Abx
DKA resolution definition
- pH > 7.3
AND - blood ketones < 0.6 mmol/L
- bicarbonate > 15 mmol/L
- Both ketonaemia and acidosis should be resolved in 24 hours, if not consult specialist
- if above criteria are met and patient is eating and drinking, switch to subcutaneous insulin
- patient should be reviewed by diabetes specialist nurse prior to discharge
Complications of DKA
Can occur from DKA itself or the treatment:
- Gastric stasis
- Thromboembolism
- Arrhythmias secondary to high/low K+
- Acute respiratory distress syndrome
- AKI
What are the causes of Hyperparathyroidism due to malignancy?
- PTHrP from the tumour e.g. squamous cell lung cancer
- Bony metastases
- Myeloma : due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, TNF) released by myeloma cells)
What are the causes of Primary Hyperparathyroidism?
- Adenoma
- Carcinoma
- Hyperplasia
H&E of Hyperparathyroidism
- painful bones, renal stones, abdominal groans and psychic groans
- corneal calcification
- shortened QT interval on ECG
- Hypertension
- polydipsia, polyuria
- depression
- anorexia, N + V
- bone pain / fracture
- Secondary to Hypercalcaemia:
- paraesthesia, muscle spasms, cramps, seizures
Investigations for Hyperparathyroidism
Bloods:
- Primary : high PTH, high calcium, low phosphate
- Secondary : high PTH, low/normal calcium, high phosphate, low vitamin D
- Tertiary : high PTH, normal/high calcium, low/normal phosphate, high ALP
Technetium-MIBI subtraction scan
XR : pepper pot skull, osteitis fibrosa cystica
Management of Malignant Hyperparathyroidism
- Initial management of hypercalcaemia is rehydration with normal saline, typically 3/4 litres a day
- Following rehydration, bisphosphonates may be used - they take 2-3 days to work and a week to take maximal effect
- Also can use calcitonin and steroids in sarcoidosis
- Loop diuretics can sometimes be used particularly in patients who can’t tolerate aggressive hydration, but this can also derange electrolytes and cause volume depletion
What is Hyperlipidemia?
- Hyperlipidemia is abnormally high levels of any or all lipids.
- e.g. fats, triglycerides, cholesterol, phospholipids or lipoproteins in the blood
What are medicines that cause dyslipidemia?
- Antipsychotics
- Corticosteroids
- Immunosuppressant drugs
What xanthomata and what are the characteristic types?
- Xanthomata are lesions in the skin filled with cholesterol and fats
- Palmar
- remnant hyperlipidemia
- less commonly seen in familial
- Eruptive (due to high triglycerides)
- Familial
- Lipoprotein lipase deficiency
What are characteristic signs of familial hypercholesteraemia?
- Tendon xanthoma
- Tuberous xanthoma
- Xanthelasma
What are Xanthelasma?
- Yellowish papules and plaques caused by localised accumulation of lipid deposits commonly seen on eyelids
- Can also be seen in patients without lipid abnormalities
Management of Xanthelasma
- surgical excision
- topical trichloroacetic acid
- laser therapy
- electrodesiccation
Investigations for Hyperlipidemia
- Total cholesterol and HDL
- Consider familial hypercholesteremia if total cholesterol is > 7.5 mmol/L and/or there is a history of premature coronary heart disease
- Lipid profile
Management of Hyperlipidemia
Primary prevention - Atorvastatin 20mg OD
- QRISK >= 10% OR most T1DM OR CKD if eGFR < 60
Secondary prevention - Atorvastatin 80mg OD
- known IHD OR cerebrovascular disease OR peripheral artery disease
Lifestyle modifications for Hyperlipidemia
- Reduced fat intake
- Physical activity
- Weight management
- Control alcohol intake
- Stop smoking
What is Diabetes Insipidus?
Production of dilute urine (hypotonic polyuria)
Causes of Cranial Diabetes Insipidus
Inadequate secretion of ADH
- Pituitary tumour/ surgery
- Traumatic brain injury
- Infection (e.g. meningitis)
- Sarcoidosis/ TB
- Haemochromatosis
Causes of Nephrogenic Diabetes Insipidus
Insensitivity to ADH
- Lithium therapy
- Electrolyte imbalance (inc. Ca2+, dec. K+)
- Idiopathic
- Ureteric obstruction
- Inherited (AVPV2 gene)
H&E of Diabetes Insipidus
- Polyuria
- Nocturia
- Polydipsia
- Dehydration
- Tachycardia, reduced turgor, dry mucous membranes
- Signs relating to cause (e.g. bitemporal hemianopia)
Investigations for Diabetes Insipidus
- U&Es - raised calcium, raised urea, low potassium, normal sodium and normal glucose
- Plasma osmolality = high
- Urine osmolality = low (>700 excludes diabetes insipidus)
- Water deprivation test
- Water restricted for 8 hours, measure plasma and urine osmolality every hour, then give desmopressin and measure urine osmolality
- STOP TEST IF BODY WEIGHT FALLS BY 3%
- Cranial: >50% rise in urine osmolality after desmopressin
- Nephrogenic: <45% rise in urine osmolality after desmopressin
Management of Diabetes Insipidus
- Treat underlying cause
- Cranial : intranasal desmopressin (lower fluid intake)
- Nephrogenic : thiazide diuretic or NSAIDs, low salt/protein diet
Management of Primary Hyperparathyroidism
- total parathyroidectomy
- conservative management offered if calcium level less than 0.25 mmol/L above upper limit AND patient is >50 years old AND no evidence of end-organ damage
- patients not suitable for surgery may be treated with cinacalcet, a calcimimetic
Management of Secondary Hyperparathyroidism
- medical therapy
- indications for surgery include bone pain, persistent pruritis and soft tissue calcifications
Management of Tertiary Hyperparathyroidism
- Excise gland or total parathyroidectomy
Causes of Secondary Hyperparathyroidism
Increased secretion of PTH in response to hypercalcaemia
- Chronic renal failure
- Vit D deficiency
Causes of Tertiary Hyperparathyroidism
Autonomous PTH secretion following secondary hyperparathyroidism
What are pituitary adenomas and the types?
Benign tumours of the pituitary gland
Non-functional - do not release hormones, can be asymptomatic
Functional - release hormones, symptoms related to excess secretion
Can also compress other parts of pituitary glands causing hypopituitarism or compress on optic chiasm causing bitemporal hemianopia
Examples of Functional Adenomas
- Acromegaly : GH
- Prolactinoma : Prolactin
- Cushing’s disease : ACTH
Investigations for Non Functional Adenomas
- Bloods to check all hormones
- Pituitary MRI
Management of Non Functional Adenomas
Microadenoma (<1cm) : observation
Macroadenoma (>1cm) without mass effect : observation + evaluation or surgery and HRT
Macroadenoma with mass effect : transsphenoidal surgery + HRT
What is Hyperprolactinaemia?
Increased prolactin - suppresses GnRH pulsatility - decreased FSH + LH
- Reduced testosterone and spermatogenesis in men
- Reduced oestrogen and progesterone in women
Causes of Hyperprolactinaemia
- Pregnancy
- Breastfeeding
- Prolactinoma
- Primary hypothyroidism (TRH usually causes prolactin release)
H&E of Hyperprolactinaemia
- Infertility/ sub fertility
- Osteoperosis
- Mass effect
- Men : ED, hypogonadism, gynaecomastia, reduced beard growth
- Women : galactorrhea, secondary amenorrhea, oligoamenorrhea
Investigations for Hyperprolactinaemia
- Pregnancy test
- TFTs
- Basal serum prolactin : >6000 mU/L confirms
- Pit MRI to confirm prolactinoma
Management of Hyperprolactinaemia
- Dopamine receptor agonists
- cabergoline
- reduce prolactin secretion and tumour size, especially if awaiting surgery
- Transsphenoidal surgery
- Sellar Radiotherapy
What is Acromegaly?
Excess GH secretion
H&E of Acromegaly
- Insidious onset and slowed progression - delayed diagnosis
- Headache and active sweating
- GH stimulates production of IGF-1
- initial screening test
- Oral glucose tolerance test used to confirm raised IGF-1 (glucose load should suppress GH)
Management of Acromegaly
Transsphenoidal surgery is first-line
If pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
- somatostatin analogue
- directly inhibits GH release
- octreotide
- effective in 50-70% of patients
- pegvisomant
- GH receptor agonist
- once daily
- very effective - decreases IGF-1 in 90% of patients
- doesn’t decrease tumour size
External irradiation is sometimes used for older patients or following failed surgical/medical treatment
What is T1DM?
Inadequate secretion of insulin due to autoimmune destruction of pancreatic beta cells
What is T2DM?
Reduced peripheral sensitivity to insulin, which leads to reduced insulin production
H&E of DM
Typically presents in <20 for T1 and >40 in T2
Polyuria and polydipsia
Type 1:
- Weight loss and fatigue
- DKA - N+V, abdo pain, kussmaul breathing and sweet-smelling breath
Type 2:
- Often asymptomatic
- on exam : acanthosis nigricans, micro/macrovascular complications
RF for T2DM
- obesity
- hypertension
- south asian/ afro caribbean
- FHx
Investigations for DM
- random glucose > 11.1
- fasting glucose > 7.0
- 2hr post prandial glucose > 11.1
- HbA1c > 48
- Diagnosis can be made if symptomatic + 1 of above OR asymptomatic + 2 above tests on different days
- Urine dip for glucose and ketones
- Anti-GAD and Islet cell antibodies - found in Type 1
Management of T1DM
- Insulin
- Monitored with capillary glucose and HbA1c
- Basal bolus regime
- long acting : glargine subcut OD
- short acting : lispro subcut pre-meal
Management of T2DM
Glycaemic control :
- Lifestyle changes
- Metformin if HbA1c > 48 despite lifestyle
a. aim for <48
b. if not tolerated switch to modified release - SGLT-2 inhibitor (if CV risk)
- If HbA1c rises to 58, add DPP-4 inhibitor, pioglitazone or sulfonylurea
- if triple therapy not effective, consider switching one drug for GLP-1 mimetic
BP control :
1. ACEi or ARB (CCB in afro caribbean)
Lipid management if QRISK > 10%
- atorvastatin 20mg OD
- atorvastatin 80mg OD if IHD/CVD/PAD
Antiplatelets if existing CVD
What is Hypoglycaemia?
Low plasma glucose (<3.6 mmol/L)
Causes of Hypoglycaemia
- Inappropriate insulin regime
- Missed meals
- Unaccustomed exercise
- Drugs (sulfonyureas, SGLT-2 inhibitors, etc.)
- Liver failure
- Insulinoma - increased ratio of proinsulin to insulin
- Addison’s disease
- Alcohol
H&E of Hypoglycaemia
<3.3 mmol/L causes autonomic symptoms:
- Palpitations (tachycardia)
- Tremors
- Sweating
- Anxiety
- Hunger
- Nausea
<2.8 mmol/L causes neuroglycopenic symptoms:
- Weakness
- Vision changes
- Confusion
- Convulsions
- Coma
Management of Hypoglycaemia
If conscious
- Oral glucose (solution/tablet) and complex carb
If consciousness impaired
- 1mg glucagon IM
- If that fails, IV dextrose (e.g. 10% glucose infusion)
