endocrinology Flashcards
What are the 7 major organs involved in the endocrine system
pituitary gland, thyroid, parathyroid, adrenal glands, pancreas, ovary and testes
What are the properties of water-soluble hormones
transport- unbound
cell interaction- bind to surface receptor
half-life- short
Clearance- fast
Are peptide hormones lipo or hydro-philic
hydrophilic
What are the properties of Fat-soluble hormones
transport- protein bound
cell interaction- diffuse into cell
half life- long
clearance- slow
Are steroid hormones lipo or hydrophilic
lipophilic
what form are peptide hormones in at different stages
Synthesis: preprohormone -> prohormone
Packaging: prohormone -> hormone
Storage: hormone
Secretion: hormone
Are thyroid hormones water soluble
Thyroid hormones are not water soluble, 99% is protein bound.
What is the process of T3 and T4 synthesis and secretion
Tyrosine molecules are incorporated with iodine to form iodothyrosines. These conjugate to give rise to T3 and T4 which are stored in colloid bound to thyroglobulin. T3 and T4 are cleaved from thyroglobulin when TSH stimulates the movement of colloid into secretory cell.
Which hormones have their receptor in the nucleus
oestrogen
thyroid hormone
vitamin D
Which class of hormone has its receptors in the cytoplasm
steriods
What are the features of vitamin D
Fat soluble
Enters cells directly to nucleus to stimulate mRNA production
Transported by vitamin D binding protein
cholesterol derivative
What are the features of adrenocortical and gonadal steroids
95% protein bound
After entering the cell, it passes to nucleus to induce response
Altered to active metabolite
Bind to a cytoplasmic receptor
What are the 5 steps of steroid action
Steroid hormone diffuse through plasma membrane and binds to receptor
Receptor-hormone complex enters nucleus
Receptor-hormone complex binds to GRE
Binding initiates transcription of gene to mRNA
mRNA directs protein synthesis
What are GREs
glucocorticoid-response elements, found in promoter regions of steroid sensitive genes
What is involved in the control of hormone secretion
Basal secretion – continuously or pulsatile
Release inhibiting factors – dopamine inhibiting prolactin, sum of positive and negative effects (GHRH and somatostatin on GH)
Releasing factors
What is involved in the control of hormone action
Hormone metabolism
Hormone receptor induction ( induction of LH receptors by FSH in follicle)
Hormone receptor down regulation
Synergism
Antagonism
What is the hypothalamo-pituitary-thyroid axis
Hypothalamus -> TRH -> anterior pituitary -> TSH -> thyroid gland -> thyroid hormones
What are the 5 functions of thyroid hormone
Accelerates food metabolism
Increases protein synthesis
Enhances fat metabolism
Brain development during foetal life and postnatal development
Growth rate accelerated
What is the endocrine role of the adrenal cortex
Produces steroids hormones:
Mineralocorticoids e.g. aldosterone
Glucocorticoids e.g. cortisol androgens
Androgens e.g. androstenedione and DHEA
What is the endocrine function of the adrenal medulla
Produces epinephrine and norephinephrine
What are the levels of BMI
<18.5 – underweight
18.5-24.9 – normal
25.0-29.9 – overweight
30.0-39.9 – obese
>40 – morbidly obese
How is BMI calculated
weight (kg) / height (m2)
What are 7 major risks of obesity
Type II diabetes
Hypertension
Coronary artery disease
Stroke
Osteoarthritis
Obstructive sleep apnoea
Carcinoma
What 4 carcinomas have an increased risk caused by obesity
Breast
Endometrium
Prostate
Colon
What is the effect of different nutrients on satiety
Highly refined sugar – quick and short satiety
Low glycaemic index foods – better
High protein – prolonged satiety
High fat – stimulate and entice people to eat more
Which region of the brain plays a central role in appetite regulation
Hypothalamus
What is the structure and action of peptide YY
36 amino acids
Structurally similar to NPY
Binds NPY receptors
Secreted by neuroendocrine cells in ileum, pancreas and colon in response to food
Inhibits gastric motility
Reduces appetite
what is NPY
Neuropeptide Y
It stimulates food intake, preferably carbohydrates
What is Cholecystokinin’s effect on appetite regulation
Receptors in pyloric sphincter
Delays gastric emptying
Gall bladder contraction
Insulin release
And via vagus – satiety
What 4 stimuli are involved in increasing appetite
Olfactory, gustatory, cognitive and visual stimuli
Which hormone stimulates food intake
Ghrelin
What is the role of stretch receptors in the stomach
increase satiety
What 4 hormones increase satiety
CCK, Glucagon like peptide-1 (GLP), insulin and Peptide YY
Define Diabetes Mellitus
A disease in which the body’s ability to produce or respond to the insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood.
Name 6 types of diabetes
Type 1
Type 2 – includes gestational and medication induced diabetes
Maturity-onset diabetes of the young (MODY)
Pancreatic diabetes
Endocrine diabetes – Cushing’s/ acromegaly
Malnutrition related diabetes
What is the pathology of diabetes
Chronic hyperglycaemia due to insulin dysfunction – can’t move glucose from blood into cells. Leads to low glucose in cells with starve of energy.
Define type 1 diabetes
an insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction.
Define type 2 diabetes
inappropriately low insulin secretion and peripheral insulin resistance
What is the disease process of diabetes
Lack of insulin drives the mobilisation of energy stores from muscles, fat and the liver
Glucose accumulates in the blood, causing hyperglycaemia
In the kidneys, the glucose reabsorption mechanism becomes saturated and glucose appears in the urine
Glucose within renal tubules draws water in by osmosis, leading to osmotic diuresis
The raised plasma osmolality stimulates the thirst centre
Over time, diabetes damages capillaries and markedly accelerates atherosclerosis
how does acromegaly cause secondary diabetes
excessive secretion of growth hormone. Insulin resistance rises.
How does cushing’s syndrome cause secondary diabetes
increased insulin resistance, reduced glucose uptake into peripheral tissues.
What is the process of drug-induced diabetes
glucocorticoids increase insulin resistance
What causes type 1 diabetes
initiated by genetic susceptibility and environmental triggers
What causes type 2 diabetes
combination of genetic predisposition and environmental factors (obesity and lack of physical activity)
What causes MODY
single gene defect altering beta cell function
What are 6 subacute clinical presentations of diabetes
Thirst (osmotic activation of hypothalamus)
Polyuria (osmotic diuresis)
Weight loss and fatigue (lipid muscle loss due to unrestrained gluconeogenesis)
Hunger (lack of useable energy source)
Pruritis vulvae and balanitis
Blurred vision (due to uptake of glucose/ water into lens)
What are 5 suggestive features of type 1 Diabetes
Onset in childhood/ adolescence
Lean body habitus
Acute onset of osmotic symptoms
Prone to ketoacidosis
High levels of islet autoantibodies
What are 3 suggestive features of type 2 diabetes
Usually presents in over 30s
Onset is gradual
Diet, exercise and oral medication can often control hyperglycaemia
What are 4 suggestive features of MODY
Parents affected with diabetes
Absence of islet autoantibodies
Evidence of non-insulin dependence
Sensitive to sulphonyl urea
What are 3 investigations for diabetes
Fasting >7mmol/L plasma glucose
Random plasma glucose >11mmol/L
HbA1c 6.5%/ 48mmol/mol
What are 3 methods of neuropathy screening for diabetes
sensation (10mg monofilament), vibration perception (tuning fork), ankle reflexes.
What are the consequences of missing a type 1 diabetes diagnosis
It can lead to fat metabolism and the formation of ketone bodies.
What is the process of ketone body production in type 1 diabetes
reduced insulin leads to fat breakdown, forming free fatty acids, which:
Impair glucose uptake
Are transported to the liver, providing energy for gluconeogenesis
Are oxidised to form ketone bodies (acetone, beta-hydroxybutyrate)
Ketone bodies dissolve in the blood and release H+, causing acidosis.
What is the process of Ketoacidosis
Absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones.
Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume
Ketones cause anorexia and vomiting
What is Diabetic Ketoacidosis (DKA) characterised by
hyperglycaemia, raised plasma ketones and metabolic acidosis
What are 4 symptoms of DKA
Polyuria and polydipsia
Nausea and vomiting
Weight loss
Abdominal pain
what are 6 signs of DKA
Hyperventilation
Dehydration
‘Fruity breath’
Hypotension
Tachycardia
Coma
What are the 4 steps in management of DKA
Rehydration
Insulin
Replacement of electrolytes (K+)
Treat underlying cause
What are 6 complications of diabetes
Leading cause of blindness in working age adults – diabetic retinopathy
Diabetic nephropathy – leading cause of end-stage renal disease
Peripheral vascular disease
Stroke
Cardiovascular disease – leading cause of mortality
Diabetic Peripheral Neuropathy – leading cause of non-traumatic lower extremity amputations
what are 4 ways that diabetes causes morbidity and mortality
Acute hyperglycaemia- metabolic emergencies, DKA, HHS
Hyperglycaemic hyperosmolar state
Chronic hyperglycemia- tissue complications
side effects of treatment- hypoglycemia
What are 4 features of Diabetic neuropathy
Pain – burning, paraesthesia
Autonomic – orthostatic hypotension, constipation, ED
Insensitivity – foot ulceration, Charcot foot, amputation
Peripheral neuropathy – glove and stocking sensory loss
What are 4 risk factors for diabetic neuropathy
hypertension, smoking, changes in HbA1c, diabetes duration
What are 3 treatment methods for diabetic neuropathy
good glycaemic control, anticonvulsants, opioids.
What are 3 features of diabetic retinopathy
Micro-aneurysms: pericyte and smooth muscle loss
Leakage: basement membrane thickening reduced junctional contact with endothelial cells
Ischaemia: pericyte loss
What is the treatment of diabetic retinopathy
laser therapy to stabilise changes, not improve sight.
What is the core aim to management of type 1 diabetes
Restore the physiology of the beta cell
What are the methods to management of type 1 diabetes
Insulin treatment (twice daily with meals)
Awareness of blood glucose lowering effect of exercise
Ability to judge CHO intake
DAFNE: dose adjustment for normal eating (reduces DKA and severe hypos)
What is the first line treatment for Type 2 diabetes
Weight loss and exercise are substantial and will reverse hyperglycaemia
What is the issue with the first line treatment for type 2 diabetes
Patients with type 2 diabetes don’t tend to respond to these lifestyle changes, due to their lifestyle choices.
What is the second line treatment for type 2 diabetes
Medication to control BP, blood glucose and lipids.
Metformin = weight loss
Metformin + sulphonyl urea but side effect of weight gain + chance of hypo
Insulin
What is Hyperglycaemic Hyperosmolar state (HHS) and who does it affect
A complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis.
unwell patients with type 2 DM
What are 6 symptoms of HHS
Weakness
Leg cramps
Vision problems
An altered level of consciousness
marked dehydration
glucose >30mmol/L.
What is the effect on ketonemia in HHS
There is no switch to ketone metabolism, so ketonemia stays <3MMOL/L AND PH >7.3.
What is the typical osmolality in HHS
> 320mosmol/kg.
What are the dangers of occlusive events in HHS
focal CNS signs, chorea, Disseminated intravascular coagulation (DIC), leg ischaemia
What is the management of HHS
Give LMWH prophylaxis to all unless contraindication
Rehydrate slowly with 0.9% saline IVI over 48h
Replace K+ when urine starts to flow
what are the 3 mechanisms for increased levels of thyroid hormone
Overproduction of thyroid hormone
Leakage of preformed hormone from thyroid
Ingestion of excess thyroid hormone
What are 5 causes of Hyperthyroidism
Grave’s disease
Toxic multinodular goitre
Toxic adenoma
Congenital hyperthyroidism
Thyroiditis
What are 7 symptoms of hyperthyroidism
Weight loss
Tachycardia
Anxiety
Heat intolerance
Sweating
Diarrhoea
Menstrual disturbance
What are 3 specific signs to graves’ disease
Diffuse goitre
Thyroid eye disease
Acropachy
What is the specific sign for adenomal hyperthyroidism
Solitary nodule
What is euthyroid hyperthyroxinemia
Euthyroid hyperthyroxinemia is defined as a condition in which the serum total T4 and T3 concentrations are increased, but the thyroid-stimulating hormone (TSH) concentration is normal and there are no clinical signs or symptoms of thyroid dysfunction.
What are 3 investigations for thyroid diseases
Thyroid function tests to confirm biochemical hyperthyroidism
Clinical history, physical signs usually sufficient for diagnosis
Supporting investigations – thyroid antibodies
What are 4 treatments for hyperthyroidism
Antithyroid drugs e.g. thionamides (carbimazole)
Beta blockers
Radioiodine
Surgery (partial/ subtotal thyroidectomy)
Define Graves’ disease
An autoimmune disease affecting the thyroid that causes hyperthyroidism and results in an enlarged thyroid.
What is the pathology of graves disease
The immune system is tricked into targeting receptors on the thyroid gland, causing it to become overactive - hyperthyroidism.
Increased levels of TSH receptor stimulating antibody (TRAb) which causes excess thyroid hormone secretion (low TSH in the blood stream, but high thyroid hormone levels (T3 and T4) due to the TRAb having the same effects as TSH on the thyroid).
What are 7 symptoms and signs of graves disease
Anxiety and irritability
A fine tremor of your hands or finger
Heat sensitivity and an increase in perspiration or warm, moist skin
Weight loss, despite normal eating habits
Enlargement of thyroid gland (goiter)
Bulging eyes – Graves’ ophthalmopathy
Thick, red skin usually on the shins or tops of the feet - Graves’ dermopathy
What is the core aim of management of graves disease
Inhibition of the production of thyroid hormones and to block the effect of the hormones on the body.
What are 5 methods involved in the management of graves disease
Radioactive iodine therapy – oral radioactive iodine. This destroys the overactive thyroid cells over time, causing the gland to shrink and to lessen symptoms gradually
Anti-thyroid medications – interfere with the thyroid’s use of iodine to produce hormones e.g. carbimazole
Beta blockers e.g. propranolol – provide rapid relief of irregular heartbeats, tremors, heat intolerance and muscle weakness
Ophthalmopathy – corticosteroids/ orbital decompression surgery
Thyroidectomy
Define primary Hypothyroidism
Subnormal activity of the thyroid gland due to intrinsic underactivity of the thyroid gland.
Define secondary hypothyroidism
Subnormal activity of the thyroid gland due to reduced stimulation of the gland caused by a deficiency of TSH due to disease of the pituitary gland
define tertiary hypothyroidism
Subnormal activity of thyroidgland due to low TRH caused by hypothalamic disease
What is the most common type of hypothyroidism, its proportion of all cases and is most common cause
Primary
>99%
Most cases due to Hashimoto’s thyroiditis (autoimmune hypothyroidism)
What are the 3 main causes of Adult primary hypothyroidism
Hashimoto’s thyroiditis
Thyroidectomy
Iodine deficiency
What is the main cause of adult secondary hypothyroidism
Pituitary tumour
What are the 3 main causes of child hypothyroidism
Neonatal hypothyroidism
Resistance to thyroid hormone
Isolated TSH deficiency
What are 14 symptoms of hypothyroidism
Fatigue, loss of energy, lethargy
Weight gain
Decreased appetite
Cold intolerance
Dry skin
Muscle pain, joint pain, weakness in the extremities
Depression
Emotional lability, mental impairment
Forgetfulness, impaired memory, inability to concentrate
Constipation
Menstrual disturbances, impaired fertility
Decreased perspiration
Paraesthesia and nerve entrapment syndromes
Blurred vision
What are 10 signs of hypothyroidism
Weight gain
Slowed speech and movements
Dry skin
Jaundice
Pallor
Coarse, brittle, straw-like hair
Loss of scalp hair, axillary hair, pubic hair, or a combination
Hoarseness
Bradycardia
Pericardial effusion
What are the differential diagnoses to hypothyroidism
Addison disease
Goiter
Chronic fatigue syndrome
Hypopituitarism
Iodine deficiency
What are the investigations for hypothyroidism
Sinus bradycardia, low pulse pressure, pericardial effusion, coronary artery disease
TSH and thyroxine tests
What are the outcomes of TSH and T3/T4 tests for primary hypothyroidism
Increased TSH, usually decreased free T4, decreased T3
T4/T3 may be below normal in positive titre of TPO antibodies in Hashimoto’s
What are the outcomes of TSH and T3/T4 tests for secondary hypothyroidism
TSH inappropriately low for reduced T4/T3 levels
What are the 3 features of hypothyroidism management
Full replacement of 100 µg thyroid hormone (Levothyroxine) – titre according to TSH
Requirements vary according to cause e.g. higher disease in thyroid ablation
Monitoring treatment
What are the 3 features of monitoring hypothyroidism treatment
Dose titrated until TSH normalises
T4 half-life is long – check levels 6-8 weeks after dose adjustment
In secondary/ tertiary hypothyroidism TSH will always be low, T4 is monitored
What is Hashimoto’s thyroiditis
Hypothyroidism due to aggressive autoimmune destruction of thyroid cells. An autoimmune thyroid disease characterised by diffuse enlargement of the thyroid and high titres of thyroid autoantibodies.
What are 5 risk factors for Hashimoto’s thyroiditis
Sex – women more likely
Age – most commonly during middle age
Heredity – family history of Hashimoto’s disease
Other autoimmune disease
Radiation exposure – (more common in Japan)
What is the pathology of hashimoto’s disease
Inflammation from Hashimoto’s disease, chronic lymphocytic thyroiditis, often leads to an underactive thyroid gland – hypothyroidism.
Activated CD4+ helper T-cells recruit CD8+ cytotoxic T-cells which destroy thyroid follicular epithelial cells
Anti-thyroid autoantibodies produced by activated B-cells may also contribute
What are 3 triggers for Hashimoto’s disease
Iodine
Infection
Smoking
What are 10 signs and symptoms of Hashimoto’s disease
Fatigue and sluggishness
Increased sensitivity to cold
Constipation
Pale, dry skin
A puffy face
Brittle nails
Hair loss
Muscle weakness
Joint pain and stiffness
Unexplained weight gain
What are the investigations for hashimotos disease
Diagnosis is based on signs and symptoms
Blood tests – thyroid hormone and TSH levels produced in the pituitary gland
Hormone test – underactive thyroid – level of thyroid hormone is low but TSH is elevated
Antibody test – Hashimoto’s disease involved the production of abnormal antibodies. Blood test confirm presence of antibodies against thyroid peroxidase (TPO antibodies).
What is the treatment for hashimotos disease
Synthetic hormones – synthetic thyroid hormone levothyroxine
Resection of obstructive goitre
What are the 5 types of Thyroid cancers and their prevalence
papillary (most common 60%), follicular (≤25%), medullary (5%), lymphoma (5%) and anaplastic (rare).
What are the 2 aetiologies for thyroid cancers
Radiation exposure is a well-documented risk factor for thyroid carcinoma, most notably papillary carcinoma.
Iodine deficiency, particularly for follicular carcinomas
What is the pathology of thyroid cancers
Epithelial tumours that originate from thyroid follicular cells.
What are the 6 clinical presentations of thyroid cancers
Thyroid carcinoma most commonly manifests as a painless, palpable, solitary thyroid nodule.
Increased rate of malignancy in males
Nodular growth
Rapid growth: ominous sign
Usually painless; sudden onset of pain more strongly associated with benign disease
Hard and fixed nodules
What are the 4 investigations for thyroid cancers
Thorough head and neck examination, including thyroid gland and cervical soft tissues
Fine-needle aspiration biopsy (FNAB)
Indirect laryngoscopy
Lab tests – serum calcitonin – elevated levels suggest medullary thyroid carcinoma
What is the management of thyroid cancers
Malignancies require surgical intervention
What are the features of papillary thyroid cancer
Younger patients
Spread – lymph nodes and lung
What is the treatment of papillary thyroid cancer
total thyroidectomy to remove non-obvious tumour. Consider node excision/ radioiodine to ablate residual cells
Give levothyroxine to suppress TSH
What are the features and treatment of follicular thyroid cancer
Middle age
Spreads early via blood (bone, lungs)
Treatment – total thyroidectomy + T4 suppression + radioiodine ablation
What are the features and treatment of medullary thyroid cancer
Sporadic (scattered) or part of MEN syndrome (multiple endocrine neoplasia)
May produce calcitonin which can be used a cancer marker
Do not concentrate iodine
Treatment – thyroidectomy + node clearance
External beam radiotherapy may prevent regional recurrence
What are the features and treatment of thyroid lymphomas
Female: male = 3:1
May present with stridor/ dysphagia
Do full staging pre-treatment (chemotherapy)
Assess histology for mucosa-associated lymphoid tissue (MALT)
What are the features and treatment of anaplastic thyroid cancers
Female: male = 3:1
Elderly
Poor response to any treatment
Excision + radiotherapy may be tried
What is Cushing’s disease
a tumour on the pituitary gland that causes the gland to produce too much ACTH, leading to high levels of cortisol production.
What is Cushing’s syndrome
an abnormal condition caused by chronic excess levels of corticosteroids (particularly cortisol) in the body due to hyperfunction of the adrenal gland (often due to the use of corticosteroid medication).
What are the two causes of Cushing’s syndrome
Iatrogenic – pharmacological use of steroids leads to increased cortisol in circulation
Cushing’s disease
What are 5 symptoms of Cushings syndrome
Weight gain
Mood change – depression, lethargy, irritability
Proximal weakness
Gonadal dysfunction – irregular menstruation, erectile dysfunction
Acne
What are 4 signs of Cushing’s Syndrome
Central obesity - round face, supraclavicular fat distribution
Skin and muscle atrophy
Purple abdominal striae
Osteoporosis
What are 6 differential diagnoses for Cushings syndrome
Alcoholism
Anorexia nervosa
Bulimia nervosa
Depression
Obesity
Pseudo-Cushing syndrome
What are the 2 investigations for Cushings syndrome
Overnight dexamethasone suppression test
If this test is positive, test for plasma ACTH
What is the likely diagnosis for undetectable ACTH in a Cushing’s syndrome patient
Tumour adenoma of the adrenal glands
How does the overnight dexamethasone suppresion test work for cushings syndrome
1mg dexamethasone at midnight, the take serum cortisol at 8am
Normally cortisol suppresses to <50nmol/L – NO suppression in Cushing’s syndrome
Management of cushing’s syndrome
Iatrogenic – stop medications if possible
Cushing’s disease – selective removal of pituitary adenoma
What is acromegaly
The abnormal growth of hands, feet and face due to overproduction of growth hormone.
What is the pathophysiology of Acromegaly
growth hormone stimulates growth of bone and soft tissue, through secretion of Insulin-like growth factor-1.
What are 10 symptoms of acromegaly
Acral enlargement (peripheries – hands and feet)
Arthralgias (joint pain)
Maxillofacial changes
Excessive sweating
Headache
Backache
Hypogonadal symptoms
Acroparaesthesia (burning, tingling sensations in the extremities)
Amenorrhoea (absence of menstruation)
Decreased libido
What are 6 signs of acromegaly
Growth of hands
Coarsening face; wide nose
Macroglossia (big tongue)
Puffy lips, eyelids and skin
Obstructive sleep apnoea
Goitre
What are 4 differential diagnoses for Acromegaly
Marfan syndrome
Precocious puberty
Prolactinoma
Gigantism
What are the 3 investigations for acromegaly
IGF-1 test, GH test, glucose tolerance test
Why cant solely GH tests be used for Acromegaly
GH cannot be relied on alone as the secretions are pulsatile and at peaks acromegalic and normal levels overlap. GH also increases during pregnancy, stress, and sleep.
What are the 3 management options for acromegaly
1st line: Pituitary surgery (trans-sphenoidal surgery) – size of the tumour and the surgeon will determine the success of the surgery
Medical therapy – dopamine agonists e.g. cabergoline
Radiotherapy
What is Conn’s syndrome
Primary hyperaldosteronism: a disease of the adrenal glands involving excess production of aldosterone (independent of the renin-angiotensin system). It can cause high blood pressure.
What is the pathology of Conn’s syndrome
Conn’s syndrome causes excess aldosterone production due to a solitary aldosterone-producing adenoma (linked to mutations in K+ channels).
Aldosterone causes an exchange of transport of sodium and potassium in the distal renal tubule. Therefore, hyperaldosteronism causes increased reabsorption of sodium and excretion of potassium.
What are the 7 symptoms of Conn’s syndrome
Often asymptomatic
Signs of hypokalaemia
Weakness
Cramps
Paraesthesia
Polyuria (excessive urine production)
Polydipsia (excessive thirst)
What are the 3 signs of Conn’s syndrome
High blood pressure
May cause headaches, blurred vision, dizziness
Low potassium levels (not reliable as some patients will have normal levels)
This may cause fatigue, numbness, increased urination, increased thirst
What are the 4 differential diagnoses of Conns syndrome
Congenital adrenal hyperplasia (autosomal recessive disorder)
Secondary hyperaldosteronism
Exogenous mineralocorticoid excess
Liddle syndrome
What are 3 investigations for Conns syndrome
Investigate for suppressed renin and increased aldosterone
Adrenal vein sampling
U&E – potassium may be low or normal
What is the management for Conns syndrome
Laparoscopic adrenalectomy
Spironolactone (25-100)mg for 4 weeks pre-op controls BP and K+.
What is secondary hyperaldosteronism
excess aldosterone production due to a high renin from decreased renin perfusion e.g. in renal artery stenosis, accelerated hypertension, diuretics, CCF or hepatic failure.
What is Adrenal insufficiency
A condition in which the adrenal glands do not produce adequate amounts of steroid hormone (mainly cortisol). (and aldosterone)
What is the pathophysiology of adrenal insufficiency
Autoimmune destruction of the entire adrenal cortex. Loss of cortex leads to reduction in ability to produce cortisol and/or aldosterone. Excess ACTH stimulates melanocytes, resulting in the pigmentation.
What is the primary cause of adrenal insufficiency
Addison’s disease
Destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency.
What is secondary adrenal insufficiency
Hypopituitarism/ long-term steroid therapy leading to suppression of the pituitary-adrenal axis.
What are 9 symptoms of adrenal insufficiency
Fatigue
Weight loss
Dizzy
Faints
Poor recovery from illness
Adrenal crisis
Headache
Abdominal pain
Diarrhoea/ constipation
What are 5 symptoms of adrenal crisis
Hypotension and cardiovascular collapse
Fatigue
Fever
Hypoglycaemia
Hyponatraemia and hyperkalaemia
What are 2 signs of adrenal insufficiency
Pigmentation and pallor
Primary – Hyperpigmentation
Secondary – no pigmentation
Hypotension
What are the 5 differential diagnoses for adrenal insufficiency
Adrenal crisis
Eosinophilia
Hyperkalaemia
Sarcoidosis
Tuberculosis
What is the investigation for adrenal insufficiency
Short ACTH stimulation test – give ACTH, if cortisol remains low then it diagnoses AI.
What parts of the history are important in diagnosis of adrenal insufficiency
Past history
TB
Post partum bleed
Cancer
Family history
Autoimmunity – most common
Congenital disease
Any previous use of steroids
What are the 3 treatment points for adrenal insufficiency
Replace the aldosterone with fludrocortisone (for primary AI)
Hydrocortisone 2/3 times daily to replace the cortisol
Mineralocorticoids to correct postural hypertension
What is diabetes insipidus
A rare metabolic disorder in which the patient produces large quantities of dilute urine and is constantly thirsty. also known as argenine vasopressin insufficiency/resistance
What is the pathology of diabetes insipidus
It is due to a deficiency of the pituitary hormone vasopressin (ADH), which regulates reabsorption of water in the kidneys. This means that the body can’t make enough concentrated urine and too much water is passed
What is Cranial diabtetes insipidus
Most common type of diabetes insipidus
Not enough AVP in the body to regulate urine production
Caused by damage to the hypothalamus/pituitary gland e.g. after infection, operation, brain tumour or brain injury.
What is nephrogenic diabetes insipidus and its causes
There’s enough AVP in the body, but the kidneys fail to respond to it.
It can be caused by kidney damage, or sometimes inherited as a problem
Congenital
Acquired - lithium (used to treat bipolar disorder) can cause nephrogenic diabetes insipidus by damaging the cells of the kidney
What are the symptoms of diabetes insipidus
Polydipsia (extreme thirst)
Polyuria (excessive urine) – up to 20litres per day in severe cases
Tiredness (having to pass urine at night)
Irritability
Difficulty concentrating
What are 5 differential diagnoses for diabetes insipidus
Histiocytosis
Hypercalcaemia
Hypokalaemia
Medullary cystic disease
Type 1 diabetes mellitus
What are 3 investigations for diabetes insipidus
Water deprivation test
Vasopressin test
MRI scan
How is the water deprivation test used to investigate diabetes insipidus
not drinking any liquid for 8 hours – in diabetes insipidus the body will still pass large amounts of dilute urine instead of small amount of concentrated urine.
How is the vasopressin test used to investigate diabetes insipidus
inject small dose AVP. If it stops urine production = cranial DI (shortage of AVP). If urine production continues = nephrogenic DI (no response to AVP)
how is an MRI scan used to investigate diabetes insipidus
view images of the brain to see if there is damage to the hypothalamus or pituitary gland.
What are the 3 management options for diabetes insipidus
Treatment not always necessary – fluid intake must be increased to compensate for excess fluid lost through urine.
Medication called desmopressin can be used to replicate the functions of AVP (cranial DI)
Nephrogenic DI often treated with thiazide diuretics, which reduce the amount of urine the kidneys produce
What is Syndrome of innapropriate secretion of ADH
The hyponatraemia and hypo-osmolality resulting from inappropriate, continued secretion or action of the ADH arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion.
What are the 5 potential causes of Syndrome of inappropriate secretion of ADH
Malignancy – lung small-cell, pancreas, prostate, thymus, or lymphoma
CNS disorders – meningoencephalitis, abscess, stroke, subarachnoid/ subdural haemorrhage
Chest disease – TB. Pneumonia, abscess
Drugs – opiates, cytotoxics
Other – trauma, major abdominal surgery, symptomatic HIV
What is the pathology of Syndrome of inappropriate secretion of ADH
Disordered hypothalamic -pituitary secretion or ectopic production of ADH.
What is the affect of Syndrome of inappropriate secretion of ADH on Na+ and osmolality
Decreased Na+ with decreased or normal urea and creatinine
Decreased plasma osmolality
Increased urine osmolality
Increased urine Na+
what are the signs and symptoms of Syndrome of inappropriate secretion of ADH
Nausea
Irritability and headache with mild dilutional hyponatraemia
Fits and coma with severe hyponatraemia
What is the 1 differential diagnosis for Syndrome of inappropriate secretion of ADH
CSW (cerebral salt-wasting syndrome) – excessive ADH secretion caused by stimulation of the hypothalamus after trauma or ischaemia.
What are the 2 investigations for Syndrome of inappropriate secretion of ADH
Full blood count
Diagnose by serum concentrations of sodium, potassium, chloride and bicarbonate
Hyponatraemia with corresponding hypo-osmolality
Concentrated urine (Na+>20mmol/L) and osmolality (>100mOsmol/Kg)
What are the 3 management options for Syndrome of inappropriate secretion of ADH
Treat the cause and restrict the fluid
Consider salt +/- loop diuretic if severe.
Vasopressin receptor antagonists - Vaptan
What is hyperparathyroidism
Excessive secretion of parathyroid hormone, usually due to a small tumour in one of the parathyroid glands. Results in hypercalcaemia. Primary is most common.
What is the pathology of hyperparathyroidism
Primary – caused by a solitary adenoma, or occasionally hyperplasia of all glands.
Secondary – caused by decreased vitamin D intake or chronic renal failure
Tertiary – occurs after prolonged secondary hyperparathyroidism, causing glands to act autonomously after undergoing hyperplastic or adenomatous change.
What is the physiology of PTH
Parathyroid hormone (PTH) is normally secreted in response to low ionized Ca2+ levels, by 4 parathyroid glands situated posterior to the thyroid. The glands are controlled by negative feedback via Ca2+ levels.
What is the pathophysiology of hyperparathyroidism
Primary – adenoma or hyperplasia provides additional secretive tissue to provide excess PTH
Secondary – parathyroid gland becomes hyperplastic in response to chronic hypocalcaemia
Tertiary – glands become autonomous, producing excess of PTH even after the correction of calcium deficiency
What are the symptoms and signs of primary hyperparathyroidism
Often asymptomatic, occasionally bones, stones, groans, moans
What are the symptoms and signs of secondary hyperparathyroidism
kidney disease, with skeletal or cardiovascular complications
What are the symptoms and signs of tertiary hyperparathyroidism
bones, stones, groans, moans
What is bones stones moans and groans in relation to hyperparathyroidism
Bones – osteitis fibrosa cystica, osteoporosis
Kidney stones
Psychic groans – confusion
Abdominal moans – constipation, acute pancreatitis
What are 5 differential diagnoses for hyperparathyroidism
Adverse drug reaction to lithium/ thiazide diuretics
Cancers producing parathyroid hormone
Leprosy
Exogenous calcium intake
Multiple endocrine neoplasms
What are the investigations and results for primary hyperparathyroidism
Increased Ca2+ and PTH
Increased Alkaline phosphatase (ALP) – from bone resorption
What are the investigations and results for secondary hyperparathyroidism
Low serum calcium
Raised PTH
What are the investigations and results for tertiary hyperparathyroidism
Raised calcium
Raised PTH
What is the management for primary hyperparathyroidism
surgical removal of adenoma.
What is the management for secondary hyperparathyroidism
calcium correction; treat underlying cause
What are 3 other management options for hyperparathyroidism
Calcium mimetic, total or subtotal parathyroidectomy
What is Hypoparathyroidism
Subnormal activity of the parathyroid glands, causing a fall in the blood concentration of calcium and muscular spasms.
What are the 4 causes of hypoparathyroidism
genetics, autoimmune (polyglandular type 1), infiltration of the parathyroid glands by iron overload (haemochromatosis), surgery (parathyroidectomy)
What is the pathology of hypoparathyroidism
PTH stimulates the activation of vitamin D, which facilitates intestinal calcium absorption, renal reabsorption of calcium as well as calcium release from bone.
What are the 7 symptoms and signs of hypoparathyroidism
increased excitability of muscles and nerves. Numbness around the mouth/ extremities, cramps,
tetany,
convulsions.
Chvostek sign- facial twitch of touching
Trousseau sign- hand and foot spasm under ischaemia
What is Pseudohypoparathyroidism
A genetic defect that causes lack of response to parathyroid hormone.
What are the 5 symptoms of Pseudohypoparathyroidism
short stature, obesity, round faces, mild learning difficulties, short fourth metacarpals
What is the treatment for Pseudohypoparathyroidism
calcium and vitamin D can reverse most of the features.
What is Pseudopseudohypoparathyroidism
a condition in which all the symptoms of pseudohypoparathyroidism are present, but the patient’s response to parathyroid hormone is normal.
What is Hypercalcaemia of malignancy
A higher-than-normal level of calcium in the blood due to a malignancy secreting parathyroid hormone-related protein.
What is the pathology of Hypercalcaemia of malignancy
Malignancies of the lung, oesophagus, skin, cervix, breast and kidney can be a cause. The tumour secretes parathyroid hormone-related protein which results in increased calcium levels.
Another cause is local osteolysis.
Main cause is primary hyperparathyroidism.
Name 16 signs and symptoms for Hypercalcaemia
Bones – osteitis fibrosa cystica, osteoporosis
Kidney stones
Psychic groans – confusion
Abdominal moans – constipation, acute pancreatitis
Weight loss
Anorexia
Nausea
Polydipsia
Polyuria
Constipation
Abdominal pain
Dehydration
Weakness
Confusion
Seizure – short QT interval on ECG
Coma
What are 2 differential diagnoses for hypercalcaemia
Hyperparathyroidism
Hypernatremia
What are the investigations and results for hypercalcaemia of malignancy
Raised Ca2+
Decreased albumin
Decreased Cl-
Alkalosis
Decreased K+
Increased PO43-
What are the 3 management options for hypercalcaemia of malignancy
Aggressive rehydration
Bisphosphonates e.g. zoledronic acid IV, usually normalize calcium within 3 days and can be given as a repeated infusion
Long term – control of underlying malignancy
what is hypocalcaemia
An abnormally low calcium concentration in the blood.
What are 5 causes for hypocalcaemia
HAVOC
hypoparathyroidism, acute pancreatitis, vit D deficiency, Osteomalacia, CKD
What are the clinical presentations of hypocalcaemia
SPASMODIC
spasms, paraesthesiae, anxious, seizures, muscle tone increase, orientation impaired, dermatitis, impetigo herpetiformis, cardiomyopathy
What are 5 differential diagnoses for hypocalcaemia
Hypoparathyroidism
Hypoalbuminemia
Metabolic alkalosis
Acute kidney injury
Acute pancreatitis
What are 5 complications of hypocalcaemia
Dysphagia
Wheezing; bronchospasm
Syncope
Congestive heart failure
Angina
What are 5 investigations for hypocalcaemia
Measure serum albumin levels to rule out hypoalbuminemia
Chvostek’s sign – tap over facial nerve and look for spasm of facial muscles
Trousseau’s sign – compression of brachial artery causes carpopedal spasm (wrist and fingers flex)
eGFR to look for chronic kidney disease
PTH and vitamin D levels
What in the history can be used to diagnose hypocalcaemia
Family history
Lack of sun exposure
Low-calcium diet
Drugs – antibiotics, loop diuretics, oestrogen
What is the management plan for hypocalcaemia
Mild symptoms
Give calcium 5mmol/6 hours, with daily plasma Ca2+ levels
Severe symptoms
10ml of 10% calcium gluconate IV over 30min.
Hypoparathyroidism – alfacalcidol
correct resp. alkalosis if thats the cause
What is hyperkalaemia
An abnormally high concentration of potassium in the blood, usually due to failure of the kidneys to secrete it.
What are the boundaries for mild, moderate and severe hyperkalaemia
Mild: 5.5-6.0mEq/L
Moderate: 6.1-7.0mEq/L
Severe: ≥7.0mEq/L
What are the 6 potential causes of hyperkalaemia
Renal impairment
Rhabdomyolysis (muscle injury – death of muscle fibres that release their contents into the bloodstream)
Metabolic acidosis
Addison’s disease (primary adrenal insufficiency)
Drugs interfering with potassium excretion e.g. ACEi
Burns
What are 7 signs and symptoms of hyperkalaemia
A fast, irregular pulse
Chest pain
Weakness
Palpitations
Light-headedness
Dyspnoea
Paraesthesia
Frank muscle paralysis
What are the 3 differential diagnoses for hyperkalaemia
Metabolic acidosis
Rhabdomyolysis
Acute tubular necrosis
What are the 4 investigations for hyperkalaemia
Plasma potassium >6.5mmol/L – emergency, needs urgent assessment
Bloods: check potassium, recheck unexpected result
ECG: tall tented T waves, small P waves, wide QRS complex and ventricular fibrillation
Urine potassium, sodium and osmolality
What is involved in the treatment of a hyperkalaemic crisis
Calcium gluconate – protects heart (prevents ventricular fib)
Insulin + dextrose (drives potassium into cells)
Salbutamol nebulised
Calcium resonium
What are the 4 management options for hyperkalaemia
Treat underlying causes, review medications
Polystyrene sulfonate resin, binds K+ in the gut, preventing absorption and bringing K+ levels down over a few days.
If vomiting – 30g enema, followed by a 9 hour colonic irrigation
Dietary potassium and loop diuretic
What is hypokalaemia
Abnormally low levels of potassium in the blood: occurs in dehydration.
What are the 7 potential causes for hypokalaemia
Diuretics - hyperaldosteronism
Vomiting and diarrhoea
Pyloric stenosis
Intestinal fistula
Cushing’s syndrome/ steroids/ ACTH
Conn’s syndrome
Alkalosis
What are 8 clinical presentations for hypokalaemaia
Muscle weakness
Hypotonia
Hyporeflexia
Cramps
Tetany (intermittent muscular spasms)
Palpitations
Light-headedness (arrhythmias)
Constipation
What are 3 differential diagnoses for hypokalaemia
Bartter syndrome (inherited defect that causes low potassium levels)
Hyperthyroidism and thyrotoxicosis
Metabolic alkalosis
What are 3 investigations for hypokalaemia
If potassium <2.5mmol/L, urgent treatment is required.
ECG: T wave inversion, prominent U wave
Urine potassium, sodium and osmolality
What is the treatment for mild hypokalaemia
Mild (>2.5mmol/L)
Oral K+ supplement
Review after 3 days
What is the treatment for severe hypokalaemia
Severe (<2.5mmol/L)
IV potassium (no more than 20mmol/h and 40mmol/L)
Do not give K+ if oliguric.
What are neuroendocrine tumours
Tumours that form from cells that release hormones into the blood in response to a signal from the nervous system.
What are 3 vital signs for diagnosing neuroendocrine tumours
Pressure on local structure e.g. optic nerves – bitemporal hemianopia
Pressure on normal pituitary – hypopituitarism
Functioning tumour – prolactinoma, acromegaly, Cushing’s disease
What is a prolactinoma
Lactotroph cell tumour of the pituitary
at what size does a microadenoma become a macroadenoma
tumour >1cm
What is the clinical presentation of a prolactinoma caused by its local effects
macroadenoma
Headache
Visual field defect (bi-temporal hemianopia)
CSF leak (rare)
What are 5 clinical presentations of prolactinomas
Menstrual irregularity/ amenorrhoea
Galactorrhoea
Infertility
Loss of libido
Low testosterone in men
What 4 investigations can be used to find prolactinomas
Ultrasound
CT
MRI
PET
What is the management plan for prolactinomas
Management is medical rather than surgery – use dopamine agonists such as cabergoline.
Remarkable shrinkage usual with macroadenoma – sight saving
Microadenoma – usually respond to small doses of cabergoline just once or twice a week
What is a Pheochromocytoma
Catecholamine (adrenaline) secreting tumour.
What is the pathology of Pheochromocytomas
Tumours of the chromaffin cells of the medulla that produce catecholamine
What are 9 clinical presentations of pheochromocytomas
Episodic
Headaches
Palpitations
Sweating
Tremor
Anxiety and nausea
Hypertension
Tachycardia
Pallor
What are 2 investigations for pheochromocytomas
24 hour urine collection for urinary catecholamines and metabolites
Plasma catecholamines
What is the management plan for pheochromocytomas
Surgery – this must be preceded by alpha and beta blocker to stagger adrenaline loss
What are carcinoid tumours
Neuroendocrine tumours that particularly affect the small bowel, large bowel or appendix.
What is the pathophysiology of carcinoid tumours
Carcinoid tumours are a group of tumours of enterochromaffin cell origin, capable of producing 5HT. They secrete bioactive compounds e.g. serotonin and Kallikrein which cause carcinoid syndrome.
GI carcinoid tumours only cause this if they metastasise to liver.
What is the clinical presentation of carcinoid tumours
Initially, few GI tumours can cause appendicitis, intussusception or obstruction. Hepatic metastases may cause RUQ pain.
then clinically present as expected based on location
What is carcinoid syndrome
the collection of symptoms some people get when a neuroendocrine tumour (usually hepatic involvement) releases hormone such as serotonin into the blood stream.
What are 4 symptoms and signs of carcinoid tumours
Bronchoconstriction
Diarrhoea
Skin flushing
Carcinoid crisis – when a tumour outgrows its blood supply, mediators flood out. Life-threatening vasodilation, hypotension, tachycardia, bronchoconstriction and hyperglycaemia occur.
What are 4 investigations for carcinoid tumours
Increased 24h urine 5-hydroxyindoleacetic acid (5HIAA)
CXR + chest/pelvis MRI/CT to help locate primary tumours
Echocardiography can be used to investigate carcinoid heart disease
Liver ultrasound – confirm metastases
What is the treatment of carcinoid syndrome
Octreotide; blocks release of tumour mediators and counters peripheral effects.
What is the management of carcinoid tumours
Loperamide for diarrhoea
Tumour resection is only cure for carcinoid tumours – vital to find primary site.
Debulking, embolisation or radiofrequency ablation of hepatic metastases can decrease symptoms
