Endocrinology Flashcards
Describe the pathophysiology, investigation and management of thyroid eye disease
Typically associated with Grave’s, but patients can be euthyroid, hypothyroid or hyperthyroid at presentation
Can be worsened by treatment, particularly radioiodine
Retro-orbital inflammation and lymphocyte infiltration results in swelling of the orbit
Eye discomfort, diplopia, exophthalmos, proptosis, lid retraction
Diagnose clinically
Treat hyper or hypothyroidism, avoid smoking, artificial tears, treat other symptoms
In later disease, high dose steroid may be used and surgery may be required
Describe symptoms of diabetes
- Glycosuria - Depletion of Energy Stores
- Tiredness, Weakness, Weight Loss, Difficulty Concentrating, Irritability
- Glycosuria - Osmotic Diuresis
- Polyuria, Polydipsia, Dry Mucous Membranes, Reduced Skin Turgor, Postural Hypotension
- Glucose Shifts - Swollen Ocular Lenses
- Blurred Vision
- Ketone Production
- Nausea, Vomiting, Abdominal Pain, Heavy/Rapid Breathing, Acetone Breath, Drowsiness, Coma
- Depletion of Energy Stores
- Weakness, Polyphagia, Weight Loss, Growth Retardation in Young
- Complications
- Macrovascular, Microvascular, Neuropathy, Infection
Define diabetes
“a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, protein and fat metabolism resulting from defects in insulin secretion, insulin action, or both”
Describe the clinical effects of vitamin D deficiency
Can be due to poor sunlight exposure, malabsorption, gastrectomy, renal disease or enzyme-inducing drugs
Can result in osteomalacia in adulthood
Failure to ossify bones in adulthood as a result of Vit D deficiency
Presents insidiously with bone pain, proximal myopathy and hypocalcaemia
Characterised by low calcium, low phosphate, high ALP, low Vit D, elevated PTH
Treat with vitamin D replacement (cholecalciferol or alfacalcidol)
Describe Latent Autoimmune Diabetes of Adulthood
Age of onset >25yrs
Obesity is rare
Insulin usually required within months or years of diagnosis
Polygenic inheritance
GAD antibodies
Describe the pathophysiology, investigation and management of hyperprolactinaemia
Can be caused by prolactin-releasing pituitary tumours
Clinical features include galactorrhoea, headaches, mass effect, visual field defects, amenorrhoea, erectile dysfunction
Diagnose with serum prolactin (usually >6000) and pituitary MRI
Remaining pituitary function should also be tested (gonadal and thyroid hormones)
Treat with dopamine agonists (e.g. cabergoline, bromocriptine) as dopamine has a negative feedback mechanism on prolactin secretion
Surgery only indicated if medical therapy fails
Describe Whipple’s triad
collection of three criteria that suggest a patient’s symptoms result from hypoglycemia that may indicate insulinoma
- Low Plasma Glucose
- Symptoms Consistent with Hypoglycaemia
- Relief of Symptoms when Glucose is Raised to Normal
Describe the treatment of hypoglycaemia
Describe the pathophysiology, investigation and management of hyperthyroidism
Most commonly due to an autoimmune disease (Grave’s)
Symptoms include diarrhoea, weight loss, sweats, heat intolerance, palpitations, tremor
Signs include tachycardia, AF, lid lag, lid retraction, goitre, bruit, thyroid eye disease, pretibial myxoedema, thyroid acropachy
Investigate with TSH (suppressed) and Free T4 (elevated)
May also consider thyroid auto-antibodies and iodine uptake scan
Manage with beta-blockers and ‘block and replace’ with carbimazole and levothyroxine simultaneously
May require radio-iodine or thyroidectomy
Describe the normal physiological role and regulation of calcium
Functions include muscle contraction, membrane stabilisation, bone growth and remodelling, enzyme co-factor, secondary signalling messenger, hormone secretion
Most calcium is found in the skeleton, some intracellularly and some extracellularly (free or albumin-bound)
Regulated chiefly by parathyroid hormone, which raises blood calcium by increasing reabsorption at the renal distal tubule; increasing osteoclast activity; and increasing Vit D synthesis which increases calcium absorption from the gut
Describe the pathophysiology, investigation and management of Kallmann’s syndrome
A cause of primary hypogonadotropic hypogonadism
Most common form of isolated gonadotropin-releasing hormone deficiency
Due to a failure of cell migration of GnRH cells to the hypothalamus from the olfactory placode
Associated with anosmia and colour blindness
May have micropenis and cryptorchidism
Familial with variable penetration (X-Linked, Autosomal Dominant or Autosomal Recessive)
Diagnosed with clinical exam (usually due to delayed puberty) and hormone profile (LH, FSH, GnRH)
Treat with testosterone
Describe the pathophysiology, investigation and management of hypothyroidism
Common primary autoimmune causes include Hashimoto’s Thyroiditis (destruction of lymphocytic and plasma cell infiltration)
Other primary causes include iodine deficiency or post-thyroidectomy
Secondary hypothyroidism arises due to hypopituitarism (low TSH)
Causes fatigue, cold intolerance, weight gain, constipation, menorrhagia, bradycardia, dry skin/hair, goitre
Diagnosed with high TSH and low T4
Manage with levothyroxine replacement
Define gestational diabetes
Carbohydrate intolerance with onset, or diagnosis, during pregnancy
Risk factors include high body mass index, previous macrosomic baby or gestational diabetes, or family history of, or ethnic prevalence of, diabetes
All women with risk factors should have an OGTT at 24 to 28 weeks
Internationally agreed criteria for gestational diabetes using 75 g OGTT:
Fasting venous plasma glucose ≥ 5.1 mmol/l, or
One hour value ≥ 10 mmol/l, or
Two hours after OGTT ≥ 8.5 mmol/l
State causes of amenorrhoea
- Primary
- Chromosomal or Genetic Abnormalities (e.g. Turners)
- Problems with Hypothalamus or Pituitary
- Secondary
- Pregnancy
- Menopause
- Chemotherapy
- Certain Medications
- PCOS
- Thyroid Problems
Describe the pathophysiology and management of Diabetic Ketoacidosis
Absolute insulin deficiency results in activation of the ketone pathway, used in starvation states
This results in acetone (ketone) production, which along with profound hyperglycaemia can be life-threatening
Presents with osmotic symptoms, weight loss, breathlessness, abdominal pain, leg cramps, N&V, confusion
Characterised by a Metabolic Acidosis, Hyperglycaemia and Urinary/Plasma Ketones
Manage with IV fluids, insulin and assess need for potassium
Follow national DKA pathway
Describe the pathophysiology and management of Hyperglycemic Hyperosmolar State
Occurs in a relative insulin deficiency
No ketoacidosis
More insidious onset
Marked dehydration and hyperglycaemia
Rehydrate with saline and give insulin if glucose does not fall with fluids alone
LMWH prophylaxis and consider K+
Describe insulinoma
A rare neuroendocrine tumour, often benign
Presents as fasting hypoglycaemia with Whipple’s triad
Test with IV insulin and measure c-peptide (should normally be suppressed but this will not happen in insulinoma)
Image with CT/MRI and endoscopic USS
Manage with excision
Describe the pharmacology of SGLT-2 inhibitors
e.g. Empagliflozin, Canagliflozin
Inhibits sodium-glucose co-transporter in the renal tubules
Blocks glucose reabsorption and promotes loss of glucose in the urine
Describe the pharmacology of Pioglitazone
Acts on PPAR receptors to increase peripheral insulin sensitivity
SE include hypoglycaemia, fractures, oedema
Describe the pathophysiology, investigation and management of Phaeochromocytoma
Rare catecholamine-producing tumours arising from sympathetic paraganglia cells (collections of chromaffin cells) in the adrenal medulla
Often associated with hard to control hypertension
Episodes of headache, palpitations, pallor and sweating
Also associated with tremor, anxiety, nausea, vomiting, chest and abdominal pain
Diagnose with at least two 24 hour urinary catecholamines, CT abdomen and MIGB scan (chromaffin seeking analogue)
Medical management with alpha-blockade (phenoxybenzamine) first, then with beta blocker (bisoprolol) if tachycardic
Followed by surgical resection
Compare and contrast type 1 and type 2 diabetes
Type 1 - Immune pathogenesis with severe insulin deficiency
Type 2 - Combination of insulin resistance and insulin deficiency
State important causes of hypercalcaemia
- PTH-Mediated (i.e. Elevated/Normal PTH)
- Primary Hyperparathyroidism
- Familial Syndromes (MEN-1, MEN-2)
- Familial Hypocalciuric Hypercalcaemia
- PTH-Independent (i.e. Undetectable PTH)
- Malignancy
- Granulomatous Disorders
- Drugs (thiazides, lithium, calcium supplements)
- Adrenal Insufficiency
- Milk-Alkali Syndrome
- Immobilisation
State signs and symptoms of hypercalcaemia
May be asymptomatic if mild
Symptoms more common when calcium >3mmol/L
Muscle Weakness, Bone Pain, Osteoporosis
Anorexia, Nausea, Constipation, Pancreatitis
Confusion, Depression, Fatigue, Coma
Shortened QTc, Bradycardia, Hypertension
Polyuria, Nephrogenic DI, Stones
Describe testosterone replacement therapy, its advantages and disadvantages
Can be given orally, IM or topically
Best option for androgen replacement in deficiency
Side effects include mood issues (aggression/behaviour changes), libido issues, increased haematocrit, acne, sweating, gynaecomastia
Testosterone is a drug of abuse in sports
List causes of Secondary Diabetes
Genetic defects of beta-cell function
Genetic defects in insulin action
Disease of exocrine pancreas (pancreatitis, carcinoma, CF, haemochromatosis)
Endocrinopathies (acromegaly, cushings)
Immunosuppressive Agents (glucocorticoids, tacrolimus, ciclosporin)
Anti-Psychotics (clozapine)
Genetic Syndromes Associated with DM (Down’s, Turner’s, Kleinfelter’s)
Define hypoglycaemia and describe symptoms
Insulin-Treated DM - <4mmol/L
Normal People - <2.8mmol/L
Autonomic - Sweating, Palpitations, Shaking, Hunger
Neuroglycopenic - Confusion, Drowsiness, Visual Disturbance
Nausea + Headache
Describe causes of hirsutism
Male pattern hair growth in women
Causes are familial, idiopathic or due to increased androgen secretion by the ovary (e.g. PCOS, ovarian cancer), adrenal (e.g. CAH, Cushing’s, cancer) or drugs (e.g. Steroids)
Manage with oestrogens (combine contraceptive pill), metformin
Clomifene can be used for infertility
State differential diagnoses for non-diabetes hypoglycaemia
Drugs
Critical Illness (hepatic/renal/cardiac failure, sepsis)
Hormone Deficiency (e.g. Cortisol)
Non-Islet Cell Tumour
Endogenous Hyperinsulinism (Insulinoma, Functional Islet Cell Disorders, Insullin Autoimmune Hypoglycaemia)
Accidental, Surreptitious, Malicious Hypoglycaemia
Describe the rationale for Continuous Subcutaneous Insulin Infusion treatment
Can potentially provide significant improvement in glycaemic control and quality of life for some people with T1DM
Potentially make it easier to achieve glucose control with less danger of severe and incapacitating hypoglycaemia
Complications include reactions, infections at cannula site, tube blockage, pump malfunction
Describe the different insulin regimens available
Insulin is a peptide, so cannot be given orally
Can be given as a once-daily basal, twice daily mix or basal-bolus therapy
Insulin pens are more convenient, accurate, discrete and less painful than conventional vial and syringes
Describe the pathophysiology, investigation and management of Primary Gondal Disease
PGD is due to testicular failure
Causes include chromosomal defects (e.g. Kleinfelters), cryptorchidism or adult leydig cell/seminiferous tubule failure (due to trauma, chemotherapy, radiotherapy or multi-system disorders)
Characterised by low testosterone, high/normal LH and FSH and normal prolactin
Manage with testosterone replacement
State the WHO diagnostic criteria for diabetes
Fasting Plasma Glucose >/= 7mmol/L
Random Plasma Glucose >/= 11.1mmol/L
One Abnormal Value if Symptomatic
Two Abnormal Values if Asymptomatic
Should not be diagnosed on the basis of HbA1c or glycosuria alone
Describe the pathogenesis of type 1 and type 2 diabetes mellitus
- Type 1 DM
- Chronic, progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion
- Type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans
- Occurs in genetically susceptible subjects and is probably by one or more environmental agents
- Type 2 DM
- Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency
- Common with a prevalence that rises markedly with increasing levels of obesity
- Most likely arises through a complex interaction among many genes and environmental factors
Describe the pathophysiology, clinical features, investigation and management of Polycystic Ovarian Syndrome
See figure for Pathophysiology
Presents with hirsutism, acne, male-pattern hair loss, acanthosis nigricans, obesity
Lifestyle modification - diet, exercise, weight loss
Oestrogen (combined oral contraceptive)
Metformin (reduces glucose intolerance and hyperinsulinaemia)
Clomifene (selective oestrogen receptor modulator)
Gonadotropin therapy
Describe the pathophysiology, investigation and management of acromegaly
Hypersecretion of growth hormone, most commonly due to a pituitary tumour
GH stimulates bone and soft tissue growth through increased secretion of insulin-like growth factor
Features include sweats and headaches, altered facial features (coarse features, macroglossia, frontal bossing, protruding jaw), spade-like hands, increased foot size, visual impairment, cardiomyopathy, increased inter-dental spaces
Diagnose with GH measurements with OGTT (glucose should suppress GH)
Measure IGF-1 and then Pituitary MRI
First line treatment is surgery
May require medical therapy such as somatostatin analogues, dopamine agonists or GH receptor antagonists
Radiotherapy may be used for residual tumour or if ongoing symptoms
Describe MODY
Maturity Onset Diabetes of the Young
1-2% of all DM
Caused by a change in a single gene (monogenic)
Autosomal dominant
Main features include <25yrs onset, runs in families from one generation to next, managed by diet, OHAs and insulin
Describe the pathophysiology, investigation and management of Primary Hyperaldosteronism
Excess production of aldosterone, independent of the RAS system, causing sodium and water retention and reduced renin release
Mostly caused by a solitary aldosterone-producing adenoma (Conn’s syndrome)
Other causes include bilateral adrenocortical hyperplasia or adrenal carcinoma
Often asymptomatic, may have hypokalaemia, weakness, cramps, paresthesia, polyuria, polydipsia, hypertension
Investigations include a raised aldosterone and aldosterone:renin ratio and suppressed renin
Confirm with a saline suppression test (2L saline over 4 hours followed by a 4h aldosterone >270pmol/L is highly suspicious)
Manage with MR antagonists or amiloride
Surgical management with unilateral laparoscopic adrenalectomy (only if adrenal adenoma)
Describe the pathophysiology, investigation and management of Congenital Adrenal Hyperplasia
Autosomal recessive disorder
Deficiency in 21-alpha-hydroxylase
Results in steroidogenic defects including aldosterone and cortisol deficiency
This means more pregnenolone is converted to the androgen DHEA
Can result in ambiguous genitalia (female) and adrenal crisis and early virilisation (males)
Managed with mineralocorticoid and glucocorticoid replacement
Describe the pathophysiology, investigation and management of Kleinfelters
Most common genetic cause of male hypogonadism
XXY
Manifests clinically at puberty
High LH and FSH, but seminiferous tubules regress and Leydig cells do not function normally
Wide clinical variation, including delayed puberty, suboptimal genital development, reduced secondary sexual characteristics, gynaecomastia, azoospermia and behavioural issues
Manage with androgen replacement, psychological support and fertility counselling
Describe the pharmacology of DPP4 inhibitors
e.g. Sitagliptin
Blocks the action of DPP4, which destroys the enzyme incretin
Increased incretin levels inhibit glucagon, which increases insulin secretion
Describe the pathophysiology, investigation and treatment of Cushing’s Syndrome/Disease
Cushing’s syndrome is the clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms
Causes include exogenous steroid use, and a pituitary adenoma (specifically known as Cushing’s disease)
Symptoms include weight gain, mood change (depression, lethargy, irritability), proximal myopathy, gonadal dysfunction, acne
Signs include central obesity, moon face, buffalo hump, skin/muscle atrophy, bruises, abdominal striae, hypertension, hyperglycaemia
Investigate with MRI for pituitary mass, raised plasma cortisol, 24hr urinary free cortisol and dexamethasone suppression test (give dexamethasone at night and measure cortisol in the morning, should normally be suppressed but will not be in Cushing’s)
Manage by stopping offending medication, surgical removal of pituitary adenoma or adrenalectomy
Describe the pathophysiology, investigation and management of adrenal insufficiency
Primary adrenal insufficiency (Addison’s disease) is rare and characterised by destruction of the adrenal cortex leads to glucocorticoid and mineralocorticoid deficiency
Causes include autoimmunity, adrenal TB, lymphoma, opportunistic infection
Symptoms include anorexia, weight loss, fatigue, lethargy, dizziness, hypotension, hyperkalaemia, abdominal pain, vomiting, diarrhoea, skin and mucous membrane pigmentation
Investigations include;
Biochemistry - hyponatraemia, hyperkalaemia and hypoglycaemia
High ACTH levels
Adrenal auto-antibodies
Renin (high) and aldosterone (low) levels
Short Synacthen Test - Measure plasma cortisol before and 30 minutes after IV ACTH injection. In normal situations, ACTH should increase cortisol levels. A normal result is a baseline of >250nmol/L and post-ACTH of >480. In Addison’s, there would be minimal cortisol response after ACTH injection
Describe the pathophysiology and management of thyroid carcinoma
Papillary, Follicular, Medullary, Lymphoma or Anaplastic
Manage with thyroidectomy with or without radiotherapy
