Endocrinology Flashcards
1
Q
Classification of Endocrine Hormones (3)
A
Peptide hormones- composed of chains of amino acids
Steroid hormones- derived from cholesterol
Amine hormones- derived from one of two amino acids (tryptophan/tyrosine)
2
Q
Hypothalamus (3)
A
Main hormones: Trophic hormones and non-trophic
Primary targets: Anterior and posterior pituitary
Main effects: Release/inhibit pituitary hormones (trophic –> ant. pituitary, non-trophic –> post. pituitary)
3
Q
Hypothalamic-Pituitary Hormones (4)
A
The hypothalamus and anterior pituitary release trophic and non-trophic hormones
Hypothalamus releases neurohormones
Posterior pituitary releases neurohormones
Anterior pituitary releases endocrine hormones
4
Q
What are the 5 Hypothalamic Releasing Hormones? (5)
A
Thyrotrophin releasing hormone (TRH)
Corticotrophin releasing hormone (CRH)
Growth hormone inhibiting hormone (GHIH)
Gonadotrophin releasing hormone (GnRH)
Prolactin releasing hormone (PRH), aka. dopamine
5
Q
What are the 2 Hypothalamic Inhibiting Hormones? (2)
A
Growth hormone inhibiting hormone- somatostatin
Dopamine- prolactin inhibiting hormone
6
Q
Define Trophic Hormone (2)
A
Govern the release of another hormone
Secreted into anterior pituitary
7
Q
Define Non-Trophic Hormones (1)
A
Travel to posterior pituitary via neuronal axons
8
Q
Hypothalamo-Pituitary Axis (2)
A
The hypothalamus and pituitary are the principal organisers of the endocrine system
Hypothalamic communication with the pituitary gland is neural and endocrine
9
Q
Compare the Anterior (5) and Posterior (5) Pituitaries
A
Anterior: -true endocrine tissue -epithelial origin -connected to hypothalamus via capillary portal system -aka adenohypophysis -makes up 2/3 of gland Posterior: -neuroendocrine tissue -neural tissue origin -neural connection to hypothalamus -secretes neurohormones made in hypothalamus -aka. neurohypophysis -makes up 1/3 of gland
10
Q
Anterior Pituitary
- main hormones (5)
- primary targets (5)
- main effects (6)
A
Prolactin–>breast–>milk production
Growth hormone (somatotrophin)–>liver–>growth factor secretion
Corticotropin (ACTH)–>adrenal cortex–>growth + metabolism
Thyrotrophin (TSH)–>thyroid gland–>cortisonal release and thyroid hormone synthesis
Follicle stimulating hormone (gonadotrophin)–>gonads–>egg/sperm production and sex hormone production
11
Q
What is Growth Hormone and Where is it Released? (5)
A
aka. somatotrophin
Promotes growth
Requires permissive action of thyroid hormones and insulin before it stimulates growth
Peptide hormone (but 1/2 of it circulates bound to carrier proteins)
Released from anterior pituitary
12
Q
Stimuli that Increase GHRH Secretion (5)
A
Actual/potential decrease in supply to cells Increased amino acids in the plasma stressful stimuli Delta sleep Oestrogen and androgens
13
Q
Growth Hormone/IGF-1 Effects on Bone (4)
A
GH stimulates pre chondrocytes in the epiphyseal plates to differentiate into chondrocytes
During differentiation the cells begin to secrete IGF-1 and to become responsive to IGF-1
IGF-1 then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage
Epiphyseal plates close during adolescence under the influence of sex steroid hormones
14
Q
Direct Effects of Growth Hormone (5)
A
Increased gluconeogenesis by the liver
Reduces ability of insulin to stimulate glucose uptake by muscle and adipose tissue
Makes adipocytes more sensitive to lipolytic stimuli
Increased blood glucose when present in excess
Increased muscle, liver and adipose tissue amino acid uptake and protein synthesis (anabolic effect)
15
Q
Growth Hormone Negative Feedback (1)
A
IGF-1 inhibits GHRH and stimulates somatostatin
16
Q
Stimuli that Increase GHIH (Somatostatin) Secretion (4)
A
Glucose
Free fatty acid
REM sleep
Cortisol
17
Q
Hypersecretion of Growth Hormone (4)
A
Usually caused by endocrine tumours
Surgery to remove tumour or somatostatin analogues to treat
Gigantism: excess GH due to pituitary tumour before epiphyseal plates of long bones close
Acromegaly: excess GH due to pituitary tumour after epiphyseal plates close, no increase in height but can still grow in other directions eg. large hands and feet
18
Q
Reduced Growth (Dwarfism) (3)
A
Deficiency of GHRH (so less GH production)
Laron Dwarfism- end organ unresponsive to GH
Pygmies have genetic mutation that impairs ability of cells to produce IGF-1 in response to GH
19
Q
What 2 Peptide Hormones are Released by the Posterior Pituitary?
A
Vasopressin (ADH)
Oxytocin
20
Q
Hypopituitarism
Aetiology (3)
A
Hypothalamus: Kallman’s syndrome (anosmia and GnRH deficiency), tumour, inflammation, infection
Pituitary stalk: trauma, surgery, tumour
Pituitary: tumour, radiation
21
Q
Hypopituitarism
Signs + symptoms (5)
A
Growth hormone deficiency: central obesity, reduced strength and balance, atherosclerosis, dry skin
LH/FSH deficiency in males: reduced libido, erectile dysfunction, hypogonadism (less hair, small testes, small ejaculate volume)
LH/FSH deficiency in females: reduced libido, amenorrhoea, osteoporosis, subfertility
TSH deficiency: hypothyroidism
ACTH deficiency: secondary hypoadrenalism (no skin pigment change as ACTH is low)
22
Q
Hypopituitarism
Investigations (3)
A
Basal hormone tests: LH + FSH (low or normal), TFT:TSH ratio (low or normal), T4 (low), cortisol (low)
Short Synacthen test
MRI pituitary fossa: look for hypothalamic/pituitary lesion
23
Q
Hypopituitarism
Treatment (5)
A
Hydrocortisone for secondary adrenal failure before any other hormones given
Thyroxine for hypothyroid
Testosterone enanthate for males or oestradiol patches/COCP for females
Gonadotrophin therapy to induce fertility
May give somatotrophin to treat GH deficiency
24
Q
Pituitary Tumours
Definition (2)
A
Almost always benign adenomas
Account for 10% of intracranial tumours
25
Pituitary Tumours
| Types (3)
Chromophobe (70%): many are non-secretory, half produce prolactin, a few produce GH (acromegaly) or ACTH (Cushing's Disease)
Acidophil (15%): secrete GH/prolactin
Basophil (15%): secrete ACTH
26
Pituitary Tumours
| Investigations (4)
MRI: defines intra- and supra-sellar extension
Hormones: prolactin, GH, ACTH, cortisol, TFT (because secondary hypothyroidism occurs as pituitary tumour invades gland), LH, FSH, short Synacthen test
Glucose tolerance test: assess for acromegaly
Water deprivation test: assess for diabetes insipidus
27
Pituitary Tumours
| Treatment (3)
Hormone replacement (must ensure give steroids before thyroxine as it could precipitate an adrenal crisis)
Transphenoidal pituitary excision
Radiotherapy for residual/recurrent adenomas
28
Acromegaly
| Aetiology (1)
99% due to pituitary tumour (acidophil)
29
Acromegaly
| Pathology (1)
Increased GH secretion leads to bone and soft tissue growth through increased secretion of IGF-1
30
Acromegaly
| Symptoms (7)
```
Acroparaesthesia (numb extremities)
Amenorrhoea
Reduced libido
Headache
Sweating
Snoring
Galactorrhoea
```
31
Acromegaly
| Signs (6)
Increased growth of hands (spade-like), jaw and feet
Coarse facial features and wide nose
Macroglossia
Skin darkening
Carpal tunnel syndrome
Signs from pituitary mass: hypopituitarism +/- local effect (reduced vision, hemianopia, fits)
32
Acromegaly
| Investigations (5)
```
High glucose
High calcium
High phosphate
OGTT: GH is normally suppressed by glucose but this doesn't occur in acromegaly
MRI pituitary fossa
```
33
Acromegaly
| Treatment (2)
Transphenoidal excision
| If surgery fails use somatostatin analogues
34
Hyperprolactinaemia
| Aetiology (3)
Excess pituitary production: pregnancy, breastfeeding, prolactinoma
Disinhibition by pituitary stalk compression: pituitary adenoma
Dopamine antagonists: eg. anti-emetics, anti-psychotics
35
Hyperprolactinaemia
| Signs + symptoms (5)
```
Amenorrhoea
Infertility
Galactorrhoea
Reduced libido
Erectile dysfunction
```
36
Hyperprolactinaemia
| Investigations (4)
Basal prolactin
Pregnancy test
TFT
MRI pituitary if other causes ruled out
37
Hyperprolactinaemia
| Treatment (2)
Dopamine agonists 1st line
| Transphenoidal surgery 2nd line (if visual/pressure symptoms are unresponsive to medical management)
38
Diabetes Insipidus
| Definition (2)
Passage of large volumes (>3L/day) of dilute urine due to impaired water resorption by the kidney
Because of reduced ADH secretion from the posterior pituitary (cranial) or because of impaired response of the kidney to ADH (nephrogenic)
39
Diabetes Insipidus
| Aetiology (2)
Cranial: idiopathic (50%), tumour, trauma, sarcoidosis
Nephrogenic: congenital, low K, high Ca, CKD
40
Diabetes Insipidus
| Signs + symptoms (4)
Polydipsia (uncontrollable and all-consuming)
Polyuria
Dehydration
Hypernatraemia
41
Diabetes Insipidus
| Investigations (6)
```
U&E
Calcium
Glucose (exclude DM)
Urine and plasma osmolality
Water deprivation test (stage 1- fluid deprivation and collect urine, stage 2- differentiate between cranial and nephrogenic, give desmopressin): primary polydipsia- urine concentrates but less than normal, cranial- urine osmolality increased after desmopressin, nephrogenic- no increase in urine osmolality after desmopressin
MRI pituitary fossa
```
42
Diabetes Insipidus
| Treatment (2)
Cranial: desmopressin
Nephrogenic: treat underlying cause
43
What Makes up the Adrenal Gland? (2)
Adrenal medulla
| Adrenal cortex
44
What does the Adrenal Medulla Secrete? (1)
Catecholamines, mainly epinephrine but also norepinephrine and dopamine
45
What do the Different Parts of the Adrenal Cortex Secrete (4)
Zona reticularis: sex hormones
Zona fasciculata: glucocorticoids (eg. cortisol)
Zona glomerulosa: mineralocorticoids (eg. aldosterone)
Steroid hormones in response to ACTH
46
What are all Steroid Hormones Derived from? (1)
Cholesterol
47
Cortisol
| Release (4)
Circadian rhythm
Preceded by ACTH release
Cortisol bursts persists longer than ACTH bursts because 1/2 life much longer
Peak levels upon waking and due to stressful stimuli
48
Cortisol
| Importance (3)
Protects brain from hypoglycaemia
Maintaining blood glucose levels
Maintaining ECF
49
Cortisol
| Actions on glucose metabolism (4)
Gluconeogenesis: enhances
Proteolysis: breakdown of muscle protein
Lipolysis: stimulates
Decreases insulin sensitivity of muscles and adipose tissue
50
What are the Side Effects of Glucocorticoid Therapy and Why? (4)
```
Increased severity and frequency of infection (because cortisol normal function suppresses immune system)
Muscle wasting (normal cortisol catabolises muscle)
Appearance of thin skin and fragile skin due to loss of percutaneous fat stores (normal cortisol causes lipolysis)
```
51
Aldosterone (6)
Mineralocorticoid
Acts on distal tubule of kidney to determine levels of minerals reabsorbed/excreted
Increased reabsorption of Na
Promotes excretion of K
Secretion of aldosterone by adrenal cortex is controlled by renin-angiotensin-aldosterone system
End effect is Na and H2O retention and K depletion, resulting in increased blood volume and increased BP
52
Cortisol
| Non-glucocorticoid actions (4)
Negative effect on Ca balance (net loss increasing bone resorption- osteoporosis)
Impairment of mood and cognition
Permissive effect on norepinephrine (vasoconstrictive, hypertension from too much)
Suppression of immune system (cortisol reduces lymphocyte count, inhibits inflammation and reduces antibody formation)
53
CRH + ACTH
| 3
Release is promoted by stress
Alcohol/caffeine/lack of sleep disinhibit the hypothalamo-pituitary-adrenal axis
Elevation of cortisol turns down the immune system
54
Withdrawing Chronic Glucocorticoid Treatment (3)
Therapeutic cortisol enhances the negative feedback on hypothalamus and pituitary, reducing release of CRH + ACTH
Loss of trophic action of ACTH on adrenal gland causes atrophy of gland
Risk of adrenal insufficiency if withdrawal too fast
55
Cushing's Syndrome (Hyperadrenalism)
| Aetiology (2)
ACTH dependent: Cushing's disease (bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma), ectopic ACTH production (SCLC or carcinoid tumour) - TOO MUCH ACTH
ACTH independent: steroids, adrenal adenoma/carcinoma- REDUCED ACTH DUE TO -VE FEEDBACK
56
Cushing's Syndrome (Hyperadrenalism)
| Symptoms (5)
Weight gain
Mood change (depression, lethargy, irritability, psychosis)
Proximal weakness
Gonadal dysfunction (irregular menses, hirsutism, erectile dysfunction)
Virilisation in females (more masculine)
57
Cushing's Syndrome (Hyperadrenalism)
| Signs (9)
```
Central obesity
Facial plethora
Moon face
Buffalo neck hump
Bruises
Purple abdominal striae
Osteoporosis
High BP
High glucose
```
58
Cushing's Syndrome (Hyperadrenalism)
| Investigations (3)
1st line: overnight dexamethasone suppression test
2nd line: 48h dexamethasone suppression test
Plasma ACTH
59
Cushing's Syndrome (Hyperadrenalism)
| Treatment (3)
Iatrogenic: stop medications
Cushing's disease: trans-sphenoidal excision of pituitary adenoma
Adrenalectomy if adrenal adenoma/carcinoma
60
Addison's Disease (Adrenal Insufficiency)
| Aetiology (2)
Primary adrenocortical insufficiency (Addison's disease): autoimmune
Secondary adrenal insufficiency: long term steroids
61
Addison's Disease (Adrenal Insufficiency)
| Pathology (2)
Primary: adrenal cortex destruction leads to glucocorticoid and mineralocorticoid deficiency, high ACTH binds to melanoreceptors causing hyperpigmentation
Secondary: long-term steroid therapy suppresses the pituitary adrenal axis and when steroids are withdrawn the body is unable to make its own glucocorticoids, but mineralocorticoids unaffected so no hyperpigmentation
62
Addison's Disease (Adrenal Insufficiency)
| Signs + symptoms (8)
```
Weight loss
Fatigue
Skin hyperpigmentation
Dizziness
Faints
Mood disturbance
Unexplained abdo pain and vomiting pigmented palmar creases and mucosa
```
63
Addison's Disease (Adrenal Insufficiency)
| Investigations (5)
```
U&E (low Na, high K) as reduced aldosterone
Blood glucose (low) as reduced cortisol
Serum calcium (high)
9am ACTH (high in Addison's, low in secondary causes)
Synacthen test (short ACTH stimulation test): plasma cortisol before and 30 mins after Synacthen, Addison's if cortisol doesn't rise
```
64
Addison's Disease (Adrenal Insufficiency)
| Treatment (2)
```
Steroid replacement (hydrocortisone daily)
Mineralocorticoid replacement (fludrocortisone)
```
65
```
Addison's Disease (Adrenal Insufficiency)
Addisonian Crisis (4)
```
Aetiology: infection, trauma, stopping long term steroids
Signs + symptoms: shock (tachycardia, vasoconstriction, postural drop), oliguria, confusion, low GCS
Investigations: cortisol, ACTH, U&E (AKI), blood + urine + sputum cultures, blood glucose, ECG (hyperkalaemia)
Treatment: IV fluids, correct hypoglycaemia, IV hydrocortisone for glucocorticoid replacement
66
Primary Hyperaldosteronism
| Aetiology (2)
Conn's syndrome: solitary aldosterone releasing adenoma
| Bilateral adrenal-cortical hyperplasia
67
Primary Hyperaldosteronism
| Pathology (1)
Excess production of aldosterone independent of the renin-angiotensin system, causing increased sodium and water retention and suppression of renin release
68
Primary Hyperaldosteronism
| Signs + symptoms (6)
```
Often asymptomatic or signs of hypokalaemia
Weakness
Cramps
Paraesthesia
Polyuria
Polydipsia
```
69
Primary Hyperaldosteronism
| Investigations (4)
U&E
Renin and aldosterone (suppressed renin, increased aldosterone)
K low
Na high
70
Primary Hyperaldosteronism
| Treatment (2)
Conn's: laparoscopic adrenalectomy and spironolactone to control BP and hypokalaemia
Hyperplasia: spironolactone
71
Phaeochromocytoma
| Epidemiology (1)
Rule of 10s: 10% malignant, 10% extra-adrenal, 10% bilateral, 10% as part of hereditary syndromes
72
Phaeochromocytoma
| Aetiology (2)
Catecholamine producing tumours arising from adrenals
| Associated with MEN 2a + 2b
73
Phaeochromocytoma
| Symptoms (1)
Classic triad: episodic headache, sweating, tachycardia
74
Phaeochromocytoma
| Investigations (3)
High WCC
Plasma and 3x24h urine for free metadrenaline and normetadrenaline
Abdominal CT/MRI for localisation
75
Phaeochromocytoma
| Treatment (1)
Surgery: alpha blocker pre-op to avoid crisis from unopposed alpha-adrenergic stimulation
76
What are the 4 types of Islet Cells and what do they Produce?
Alpha cells: glucagon
Beta cells: insuline
Delta cells: somatostatin
F cells: pancreatic polypeptide
77
How is Insulin Synthesised and Stored? (4)
Synthesised as preproinsulin which is then converted into proinsulin in the endoplasmic reticulum
Proinsulin is then packaged as granules in secretory vesicles
Within the granules the proinsulin is cleaved to give insulin and C-peptide
Insulin is stored in this form until the B cells are activated
78
What Stimuli Increase Insulin Release? (5)
```
Increased BG
Increased amino acid in the plasma
Glucagon
Incretin hormones controlling GI secretion and motility (eg. gastrin, secretin, CCK)
Vagal nerve activity
```
79
What Stimuli Inhibit Insulin Release? (4)
Low BG
Somatostatin
Sympathetic alpha2 effects
Stress (eg. hypoxia)
80
How Does the Autonomic Nervous System Innervate Islet Cells? (2)
Increased parasympathetic activity (vagus)--> high insulin and high glucagon (to a lesser extent), in association with the anticipatory phase of digestion
Increased sympathetic activation promotes glucose mobilisation --> high glucagon, high epinephrine and insulin inhibition
81
Explain the Primary Action of Insulin (2)
Binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues to increase glucose uptake by these tissues
Insulin stimulates the mobilisation of specific glucose transporters (GLUT-4)
82
What are some additional actions of insulin? (6)
Inhibits catabolism by:
- high glycogen production by muscle and liver
- high amino acid uptake by muscle
- high protein synthesis and inhibits proteolysis
- stimulates lipogenesis and inhibits lipolysis
- inhibits gluconeogenesis enzymes in liver
83
How Does the Liver take up Glucose? (3)
The liver isn't an insulin-sensitive tissue
Liver takes up glucose by GLUT-2, which are insulin independent
Glucose enters down a concentration gradient
84
Explain the Mechanism of Control of Insulin Secretion by BG? (5)
B-cells have a specific type of K channel sensitive to ATP within the cell: KATP channel
When glucose is abundant it enters cells through GLUT and metabolism increases
Increases ATP within cell causing KATP to close
Intracellular K rises, depolarising the cell
Voltage-dependent Ca channels open and trigger insulin vesicle exocytosis into the circulation
85
How is BG Maintained? (2)
Glycogenolysis- synthesising glucose from glycogen
| Gluconeogenesis- synthesising glucose from amino acids
86
What is the Half Life of Insulin? Where is Insulin Degraded?
5 minutes
| In liver and kidneys
87
How is Excess Glucose Stored? (2)
Glycogen in liver and muscle
| Triacylglycerols in liver and adipose tissue
88
Actions of Glucagon (6)
Opposes action of insulin
Part of glucose counter-regulatory control system
Most active in the post-absorptive state
Receptors are G-protein coupled receptors linked to cAMP system
When activated, phosphorylate specific liver enzymes
Results in: increased glycogenolysis, increased gluconeogenesis, formation of ketones from fatty acids (lipolysis), elevated blood glucose
89
Which Stimuli Promote Glucagon Release? (5)
```
Low BG
High amino acids- prevents hypoglycaemia following insulin release in response to amino acids
Sympathetic innervation and epinephrine
Cortisol
Stress, eg. exercise
```
90
Which Stimuli Inhibit Glucagon Release? (4)
Glucose
Free fatty acids and ketones
Insulin
Somatostatin
91
What Happens to Insulin and Glucagon if BG Changes? (2)
High glucose --> high insulin and low glucagon
| Low glucose --> high glucagon and low insulin
92
What Effect does Amino Acid Concentration Have on Insulin and Glucagon? (2)
Amino acids --> high insulin --> low BG
| Amino acids --> high glucagon --> high BG
93
Type 1 Diabetes
| Aetiology (1)
HLA DR3+/-DR4 (>90%)
94
Type 1 Diabetes
| Secondary causes of diabetes (3)
Pathological process damaging pancreatic cells: chronic pancreatitis, pancreatic cancer, CF, haemochromatosis
Drugs: corticosteroids, anti-HIV drugs
Endocrine: Cushing's, acromegaly, hyperthyroidism
95
Type 1 Diabetes
| Latent autoimmune diabetes of adults (LADA) (3)
Form of type 1
Present later in life and misdiagnosed as type 2
Slower progression to insulin dependence
96
Type 1 Diabetes
| Pathology (2)
Autoimmune disruption of B-cells = unable to produce insulin
Means unable to utilise glucose in peripheral muscles and adipose, which stimulates counter-regulatory hormones to promote gluconeogenesis, glycogenolysis and ketogenesis
97
Type 1 Diabetes
| Signs + symptoms (7)
```
Polyuria
Polydipsia
Unexplained weight loss
Blurred vision
Lethargy
DKA/ketones on breath
Low-grade infections eg. thrush
```
98
Type 1 Diabetes
| Signs + symptoms in children <5 (6)
```
Return to bedwetting in a previously dry child
Heavier nappies
Candidiasis (oral/vulval)
Constipation
Recurring skin infections
Irritability
```
99
Type 1 Diabetes
| Investigations (3)
Symptoms + one diagnostic lab glucose (randome >11.1 mmol/l or fasting >7 mmol/l)
Two diagnostic lab glucose results on 2 separate occasions (could use oral glucose tolerance test- >11.1 2h after 75g oral glucose load)- don't need symptoms
HbA1c >48mmol/l indicates hyperglycaemia over preceding 3 months (don't need symptoms)
100
Type 1 Diabetes
| When HbA1c can't be used (7)
```
Haemoglobinopathies
Haemolytic anaemia
Untreated iron deficiency anaemia
Suspected gestational diabetes
Children
CKD
Medications that cause hyperglycaemia eg. steroids
```
101
Type 1 Diabetes
| Education (6)
Carb counting: dose adjustment for normal eating
Measure glucose before and after exercise
Travel: diabetes ID, take double quantities and split them up in case one lost
Driving: inform DVLA for restricted licence if on insulin, check levels before driving and every 2h on long journeys, if >1 severe hypo inform DVLA and stop driving
Alcohol: check levels before drinking, not empty tummy
Training on hypo management, monitoring, injection technique, sick day rules (never miss insulin)
102
```
Type 1 Diabetes
Insulin treatment (4)
```
Rapid-acting insulin analogues- at start of meal or just after
Short acting insulin
Intermediate acting insulin
Long acting insulin analogues- no awkward peak so good if overnight hypos are a problem
103
```
Type 1 Diabetes
Additional Treatment (3)
```
Metformin (add in if BMI >25)
Statins if >40, established nephropathy, other cardiovascular risk factors
Monitoring: annual retinal and foot screening
104
Type 2 Diabetes
| Pathology (3)
Relative deficiency of insulin due to excess of adipose tissue
Peripheral tissues become insensitive to insulin (abnormal response by receptors or reduced numbers)
B-cells remain intact, may even be hyperinsulinaemia
105
```
Type 2 Diabetes
Risk factors (9)
```
```
Strong family history
Obesity
Black/Asian ethnicity
History if gestational diabetes
Poor diet
Steroids
Statins
PCOS
Inactivity
```
106
Type 2 Diabetes
| Signs + symptoms (4)
Asymptomatic (often incidental finding)
Polydipsia
Polyuria
Acanthosis nigricans (hyperpigmentation in body folds)
107
Type 2 Diabetes
| Investigations (4)
Random plasma glucose >11.1 mmol/l
HbA1c >48 mmol/mol
Fasting plasma glucose >7mmol/l
Confirmed by 1 test if symptomatic or 2 on separate occasions if asymptomatic
108
Type 2 Diabetes
| Treatment (6)
Lifestyle modification: weight loss (aim 5-10%, low carb and sugar), BP (target <140/80 or <130/80 if end kidney/eye/cerebrovascular damage) with lifestyle advice but if not improved in 2 months then ACE-i (if black CCB/diuretic), atorvastatin if cVS risk
Driving: same as type 1 if sulfonylurea/insulin
HbA1c target: monitor 3-6 months until stable then 6
Metformin 1st line if Hba1c >48mmol/l
If HbA1c >53 16 weeks later: sulfonylurea --> SGLT-2 inhibitor/DPP-4 inhibitor or thiazolidinediones
3rd line: triple therapy then try insulin
109
Type 2 Diabetes
| Maturity Onset Diabetes of the Young (MODY) (1)
Rare autosomal dominant form of type 2 diabetes
110
Diabetes Medication
| Biguanides (metformin) (5)
Mechanism: increased insulin sensitivity and reduced hepatic gluconeogenesis
Contraindications: acute metabolic acidosis, general anaesthesia (withold on day)
Caution: renal impairment (risk of lactic acidosis)
Side effects: GI upset, lactic acidosis
Interactions: excessive alcohol increases risk of lactic acidosis
111
Diabetes Medication
| Sulfonylureas (eg. glicazide, glimepiride) (3)
Mechanism: stimulate pancreatic B-cells to secrete insulin
Cautions: renal impairment (can cause hypo), hepatic impairment, pregnancy and breastfeeding (risk of neonatal hypo)
Side effects: hypos, increased weight, GI upset, hypersensitivity (rash)
112
Diabetes Medication
| Thiazolidinediones (Glitazones) (4)
Mechanism: activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
Contraindications; hepatic impairment, pregnancy and breastfeeding
Side effects: hypos, weight gain, fluid retention, liver dysfunction, GI upset, fractures, impotence
Caution: CV risk, risk of fractures
113
Diabetes Medication
| SGLT-2 inhibitors (glifozins) (5)
Mechanism: inhibit resorption of glucose in kidney by SGLT-2 in the proximal tubule
Contraindications: renal impairment, pregnancy and breastfeeding
Caution: CV dsiease, elderly, hypotension
Side effects: weight loss, GU infection, thirst, polyuria, DKA at only mildly raised glucose levels
Interactions: anti-hypertensives
114
Diabetes Medication
| DPP-IV Inhibitors (gliptins eg. sitagliptin) (4)
Increases incretin (GLP-1 and GIP) levels
Contraindications: pregnancy and breastfeeding
Caution: renal/hepatic impairment, history of pancreatitis
Side effects: hypos, GI upset, oedema, increased risk of pancreatitis
115
Diabetes Medication
| GLP-1 Analogues (eg. liraglutide) (4)
Mechanism: GLP-1/incretin is released by small intestine in response to oral glucose and increased insulin secretion and inhibit glucagon synthesis, also causes weight loss
Contraindications: pregnancy and breastfeeding, GI disease
Caution: elderly, hepatic impairment
Side effects: hypos, N&V, pancreatitis, weight loss
116
Hypoglycaemia
| Definition (1)
Plasma glucose <3mmol/l
117
Hypoglycaemia
| Aetiology (5)
```
Too much insulin
Sulfonylurea
Inadequate food intake/fasting
Exercise
Alcohol
```
118
```
Hypoglycaemia
Risk factors (7)
```
```
Tight glycaemic control
Long duration of diabetes
Cognitive impairment
Extremes of age
Renal/hepatic impairment
Inadequate monitoring
Reduced carbohydrate intake: coeliac disease, gastroenteritis, alcohol
```
119
Hypoglycaemia
| Pathology (2)
Hyperinsulinaemia leads to a lack of glucose in blood travelling to the brain, causing neurological symptoms
Sympathetic response due to adrenaline release
120
Hypoglycaemia
| Edinburgh Hypoglycaemia Scale (3)
Autonomic: sweating, palpitations, shaking, hunger
Neuroglycopenic: confusion, drowsiness, odd behaviour, speech difficult, incoordination
General malaise, headache, nausea
121
Hypoglycaemia
| Types of hypoglycaemia (2)
Type 1s usually get fasting hypos (insulin/sulfonylurea induced or exercise, missed meal)
Type 2s usually get post-prandial hypos (prolonged OGTT)
122
Hypoglycaemia
| Non-diabetic causes (6)
```
Drugs: B-blockers
Pituitary insufficiency
Liver failure
Addison's disease
Islet cell tumours: insulinoma
Dumping syndrome post gastric/bariatric surgery (post-prandial)
```
123
Hypoglycaemia
| Treatment (3)
Treat with oral sugar and a long-acting starch (eg. toast)
If can't swallow, 25-50ml 50% glucose IV with 0.9% saline flush (prevents phlebitis)
Glucagon IM if no IV access (short duration of effect so repeat 20 mins later)
124
Diabetic Ketoacidosis
| Pathology (4)
Unable to utilise glucose in adipose and muscle tissues causing release of glucagon, adrenaline, cortisol and growth hormone
Glucagon promotes glycogenolysis, gluconeogenesis and ketogenesis in the liver leading to hyperglycaemia
Accumulation of ketone bodies --> metabolic acidosis
Osmotic diuresis causes electrolyte shifts + fluid depletion (usually hyperkalaemia when admitted but becomes hypo when insulin given
125
```
Diabetic Ketoacidosis
Risk factors (3)
```
Type 1 DM
Inadequate insulin
Infection
126
Diabetic Ketoacidosis
| Symptoms (8)
```
Onset over hours
Polyuria
Polydipsia
Weight loss
Weakness
N&V
Abdo pain
SOB
```
127
Diabetic Ketoacidosis
| Signs (7)
```
Dry mucous membranes
Sunken eyes
Tachycardia
Hypotension
Sweet smelling ketotic breath
Altered mental state
Sighing deep breathing (Kussmaul hyperventilation)
```
128
Diabetic Ketoacidosis
| Investigations (8)
```
ECG
CXR
Urine dipstick (ketonuria)
Capillary + lab glucose (>11.1mmol/l)
Ketones (blood): >3mmol/l
VBG: blood pH <7.3
Bicarbonate <15 mmol/l
High anion gap
```
129
```
Diabetic Ketoacidosis
Severe DKA (9)
```
```
Blood ketones >6mmol/l
Bicarbonate <5mmol/l
pH <7
Hypokalaemia on admission
GCS <12
SpO2 <92%
BP <90
Pulse >100 or <60
Anion gap >16
```
130
Diabetic Ketoacidosis
| Treatment (5)
If SBP <90: give 500ml NaCl 0.9% IV over 10-15 mins, if SBP >90: give NaCl 0.9% IV at rate that replaces deficit (maintenance) (both with KCl unless anuria)
IV insulin fixed rate of 0.1 units/kg/hour
Monitor blood ketone and glucose concentrations hourly and adjust rate accordingly
Once blood glucose concentration falls below 14 mmol/l, give glucose 10% IV + NaCl 0.9%
Continue infusion until blood ketone conc. <0.5mmol/l, pH >7.3 and patient can eat and drink, then give subcut fast acting insulin and meal
131
Diabetic Ketoacidosis
| Complications (3)
Cerebral oedema (may be due to cerebral hypoperfusion and subsequent reperfusion)
Hypokalaemia
Hypoglycaemia
132
Hyperglycaemic Hyperosmolar State (HHS)
| Epidemiology (2)
Elderly
| Type 2
133
Hyperglycaemic Hyperosmolar State (HHS)
| Aetiology (5)
Illness: MI, infection, stroke, AKI, acute abdo, pancreatitis, hyperthyroidism
Medication: metformin during intercurrent illness, diuretics, B-blocker
Substance misuse: alcohol, cocaine
Poor diabetic control/compliance
May be 1st presentation of diabetes
134
Hyperglycaemic Hyperosmolar State (HHS)
| Pathology (3)
Hyperglycaemia leads to osmotic diuresis and renal losses of water in excess of sodium and potassium
Severe volume depletion leads to increased serum osmolality leading to blood hyperviscosity
Hypertonicity leads to preservation of intravascular volume so patient may not look dehydrated
135
```
Hyperglycaemic Hyperosmolar State (HHS)
Risk factors (6)
```
```
Older
Type 2 DM
Nursing home residents/live alone
Dementia
Sedative drugs
Immunosuppression/steroids
```
136
Hyperglycaemic Hyperosmolar State (HHS)
| Symptoms (8)
```
Generalised weakness
Leg cramps
Visual impairment
Bedbound
Lethargy
Confusion
Seizures
Coma
```
137
Hyperglycaemic Hyperosmolar State (HHS)
| Signs (3)
Increased respiratory rate to lower metabolic acidosis
Raised blood urate: sunken eyes, limb weakness
Severe hypovolaemia: tachycardia and/or hypotension, reduced turgor
138
Hyperglycaemic Hyperosmolar State (HHS)
| Investigations (3)
Hyperglycaemia >30 mmol/l WITHOUT hyperketonaemia (<3 mmol/l) or acidosis (pH >7.3, bicarb >15 mmol/l)
Osmolality (measure serum osmolality: 2Na + glucose + urea
Hypovolaemia
139
Hyperglycaemic Hyperosmolar State (HHS)
| Treatment (4)
Fluid replacement should be low to prevent acute heart failure
May require potassium replacement
Insulin: low dose when glucose no longer falling with IV fluids alone or significant ketonaemia
May need to replace magnesium + phosphate as hypos are common
140
Hyperglycaemic Hyperosmolar State (HHS)
| Complications (6)
```
Cerebral oedema
Arterial/venous thrombosis
Foot ulceration
ARDS
Multi-organ failure
Rhabdomyolysis
```
141
Diabetic Foot Disease
| Aetiology (3)
Neuropathy (injury/infection over pressure points)
Ischaemia (critical toes +/- absent dorsalis pedis pulses and worse outcome)
Mixed neuropathy + ischaemia
142
```
Diabetic Foot Disease
Risk factors (3)
```
Peripheral arterial disease (smoking, hypertension, hyperlipidaemia)
Previous ulceration
Joint deformity
143
Diabetic Foot Disease
| Signs + symptoms (5)
Neuro-ischaemia: critical toes, absent dorsalis pedis, cold
Neuro-ischaemic ulcers: painful, punched out lesions at foot margins and pressure points
Neuropathy: loss of protective sensation in stocking distribution, absent ankle jerks, warm dry skin
Neuropathic ulcers: painless, punched out, injury + infection over pressure areas
Neuropathic deformity (Charcot joint): swelling, instability, loss of arch, claw toes
144
Diabetic Foot Disease
| Investigations (4)
Neuropathy: clinical assessment with monofilament
Ischaemia: clinical, ABPI, doppler, angiography
Bony deformity: X-ray
Infection: swabs, blood cultures, X-ray for osteomyelitis
145
Diabetic Foot Disease
| Treatment (4)
Conservative: daily foot inspection, footwear, regular podiatry, wound debridement and dressings
Medical: IV antibiotics for cellulitis, TCAs for painful neuropathy
Absolute indications for surgery: abscess/deep infection, spreading infection, gangrene
Vascular (angioplasty, stents, amputation) or orthopaedic (excision and drainage of abscess) surgery
146
Diabetic Neuropathy
| Aetiology (1)
Metabolic and microvascular damage to vasa nervorum
147
Diabetic Neuropathy
| Signs + symptoms (4)
Symmetric sensory polyneuropathy and glove and stocking tingling, numbness and pain
Mononeuritis multiplex: usually CNIII/IV
Amyotrophy: painful wasting of quads and other pelvifemoral muscles
Autonomic neuropathy: postural hypo, reduced cerebrovascular autoregulation, urinary retention, erectile dysfunction, diarrhoea
148
Diabetic Neuropathy
| Treatment (4)
Symmetrical sensory polyneuropathy: 1st paracetamol, 2nd amitryptiline
Mononeuritis multiplex: immunosuppression (corticosteroids)
Amyotrophy: usually just gradual (often incomplete) improvement
Autonomic neuropathy: codeine for diarrhoea, sidafenil for ED, fludrocortisone for BP
149
Diabetic Retinopathy
| Aetiology (1)
Microvascular injury to retinal arteries leads to injury to retinal neuromas
150
Diabetic Retinopathy
| Pathology (4)
Increased blood flow to retinal arteries due to hyperglycaemia causes retinal capillary leakage which leads to intraretinal haemorrhage, cholesterol exudate deposition and retinal oedema
Macula may become involved causing reduced central vision
Occlusion of retinal capillaries causes micro-aneurysms, cotton wool spots, intra-retinal microvascular damage and ultimately proliferative diabetic retinopathy
Neovascularisation is due to VEG-F release in response to hypoxia and these new vessels form on the disc and at ischaemic areas may be proliferative
151
Diabetic Retinopathy
| Findings on annual retinal screening (3)
Background retinopathy: microaneurysms (dots) , haemorrhages (blots), hard exudates (fat deposits)
Pre-proliferative retinopathy: cotton wool spots eg. infarcts, haemorrhages, venous bleeding
Proliferative retinopathy: new vessel formation (urgent referral)
152
Diabetic Retinopathy
| Treatment (3)
Pan-retinal laser photocoagulation: stops production of angiogenic factors from the ischaemic retinopathy
Anti-VEGF (intra-vitreal)
Vitrectomy
153
Diabetic Retinopathy
| Complications (5)
```
Vitreous haemorrhage
Cataract
Rubeosis iridis (new vessels on iris, occurs late and may lead to glaucoma)
Macular oedema
Visual field loss
```
154
Diabetic Nephropathy
| Pathology (5)
High glucose and high glomerular pressure result in mesangial expansion and a transient increase in GFR
Mesangial expansion gradually leads to microalbuminuria which causes nephropathy (low GFR and high proteinuria)
Fibrosis which eventually leads to Kimmelesteil-Wilson nodules which are the hallmark of diabetic glomerulosclerosis
Increased glomerular basement membrane width, diffuse mesangial sclerosis, microaneurysm and arteriosclerosis
Hypertension aggravates the process via mesangial stress
155
Diabetic Nephropathy
| Signs + symptoms (1)
Normally asymptomatic until late stages
156
Diabetic Nephropathy
| Investigations (3)
Annual screening for microalbuminuria with specialised dipstick
24h urinary collection
Urinary albumin creatinine ratio
157
Diabetic Nephropathy
| Treatment (1)
Start ACE-i or ARB even if BP normal to reduce intraglomerular pressure and proteinuria
158
Thyroid Hormone Synthesis (4)
Tyrosine and iodide obtained from diet
Follicular cells manufacture enzymes required for thyroid production, manufacture thyroglobulin and actively concentrate iodide from the plasma
Enzymes and thyroglobulin are packaged into vesicles and exported to the colloid along with iodide
Thyrosine and iodide are combined to form thyroid hormones by thyroid peroxidase enzymes
159
Thyroid Hormone Release (3)
In response to TSH, follicular cells take back up portions of colloid which form vesicles inside the cell and proteolytic enzymes cut thyroglobulin to release thyroid hormones
T3 + T4 are lipid soluble so pass through cell membrane to the plasma to bind to thyroxine binding globulin (TBG)
Hypothalamus (TRH) --> ant. pituitary (TSH) --> thyroid (T3+T4)
160
Thyroid Hormone Circulation (2)
TBG has higher affinity for T4 (6 day 1/2 life) than T3 (1 day 1/2 life)
There is 50x more T4 than T3 in plasma but TH receptors inside cells have a much higher affinity to T3 so it is more physiologically active
161
Thyroid Hormone Regulation (6)
TRH released from hypothalamus in response to stimuli, eg. cold/exercise/pregnancy
TRH stimulates ant. pituitary to release TSH
Thyroid hormones are subsequently released from the thyroid gland
-ve feedback: high levels of thyroid hormones in blood inhibit TRH + TSH release
Somatostatin inhibits TSH
Glucocorticoids inhibit TSH
162
Thyroid Hormone Function (5)
TH binds to nuclear receptors in target cells and change transcription and translation to alter protein synthesis
Raises metabolic rate and promotes thermogenesis
Increased proteolysis
Increased
lipolysis
Stimulates growth hormone receptor expression
163
```
Hyperthyroidism
Primary hyperthyroidism (3)
```
```
Grave's Disease (2/3 cases, typical age 40-60)
Toxic multinodular goitre (usually in elderly, nodules secrete TH)
Toxic adenoma (solitary nodule producing T3 + T4)
```
164
```
Hyperthyroidism
Secondary hyperthyroidism (3)
```
TSH secreting pituitary adenoma
Gestational thyrotoxicosis
B-hCG secreting tumour
165
Hyperthyroidism
| Symptoms (10)
```
Diarrhoea
Weight loss
Increased appetite
Sweats
Overactive
Heat intolerance
Palpitations
Tremor
Irritability
Oligomenorrhoea +/- infertility
```
166
Hyperthyroidism
| Signs (8)
Pulse: fast/irregular
Warm, moist skin
Fine tremor
Palmar erythema
Thin hair
Lid lag (eyelid lags behind eyes descent as patient watches your finger slowly descend
Lid retraction (exposure of sclera above iris)
Goitre, thyroid nodules or bruit depending on the cause
167
Hyperthyroidism
| Specific Grave's Disease signs (3)
Eye disease: exopthalmos (protruding eye), proptosis (eyes protrude beyond orbit), opthalmoplegia
Pretibial myxoedema: oedematouus swellings above lateral malleoli
Thyroid acropachy: extreme manifestation with clubbing and painful finger and toe swelling
168
Hyperthyroidism
| Investigations (7)
Primary hyperthyroidism: low TSH, high T4/T3
Secondary hypothyroidism: high TSH, high T4/3
ESR: high
Ca: high
LFT: high
Technetium 99 isotope scan: increased uptake in Grave's disease, decreased uptake in thyroiditis (which causes hypothyroidism but there may be a thyrotoxic phase first)
Check thyroid antibodies
169
Hyperthyroidism
| Treatment (4)
B-blocker for symptom control
Anti-thyroid medication: carbimazole (can either do titration based on TFTs o do block-replace by adding in thyroxine)
Radioiodine (most become hypothyroid post treatment, must avoid pregnant women and children)
Thyroidectomy (could damage recurrent laryngeal nerve- hoarse voice)
170
Hyperthyroidism
| Complications (4)
Heart failure
Angina
AF
Thyroid storm: extreme manifestation of thryotoxicosis often precipitated by intercurrent factors eg. infection, abrupt withdrawal of antithyroid medication, causes hyper-pyrexia, tachycardia and reduced GCS
171
Hypothyroidism
| Aetiology (6)
Primary atrophic hypothyroidism (autoimmune hypothyroidism)
Hashimoto's thyroiditis (autoimmune hypothyroidism, goitre)
Iodine deficiency
Post thyroidectomy or radioiodine treatment
Drugs: carbimazole, amiodarone, lithium
Secondary hypothyroidism: hypopituitarism (not enough TSH)
172
Hypothyroidism
| Symptoms (7)
```
Lethargy
Low mood
Cold intolerance
Weight gain
Constipation
Menorrhagia
Reduced memory/cognition
```
173
Hypothyroidism
| Signs (6)
```
Slow reflexes
Dry hair/skin
Cold hands
Goitre
Bradycardia
Severe hypothyroidism: myxoedema (subcutaneous tissue swelling, usually around eyes and dorsum of hand- can cause carpal tunnel syndrome)
```
174
Hypothyroidism
| Investigations (4)
Primary: High TSH , low T4/T3
Secondary: Low TSH, low T4/T3
Thyroid antibodies: anti-thyroid peroxidase antibodies
FBC: macrocytic anaemia
175
Hypothyroidism
| Treatment (1)
Levothyroxine
176
Thyroid Eye Disease
| Pathology (1)
Autoimmunity leads to inflammatory response and periorbital oedema
177
Thyroid Eye Disease
| Symptoms (6)
```
Eye discomfort
Grittiness
Increased tear production
Diplopia
Reduced acuity
Afferent pupillary defect (optic nerve compression)
```
178
Thyroid Eye Disease
| Signs (6)
Exopthalmos (appearance of protruding eyes)
Proptosis (eyes protrude beyond orbit- look from above)
Conjunctival oedema
Corneal ulceration
Papilloedema
Loss of colour vision
179
Thyroid Eye Disease
| Treatment (3)
Treat hypo/hyper-thyroidism
Mild: artificial tears, elevation of head when sleeping to reduce periorbital oedema
Moderate-severe: IV methylprednisolone, surgical decompression, eyelid surgery
180
Thyroid Lumps
| Differentials (2)
Benign: diffuse goitre, multinodular goitre (de Quervain's), subacute lymphocytic thyroiditis, follicular adenoma, thyroid cyst
Malignant: thyroid cancer (10% of solitary thyroid nodules are malignant)
181
Thyroid Lumps
| History (3)
Features of lump: swelling, tenderness, onset
Associated symptoms: hypo/hyperthyroidism, pressure symptoms
Past or family history of thyroid problems or autoimmune disease
182
Thyroid Lumps
| Examination (2)
Features of hypo/hyperthyroidism
Lump: diffuse goitre, multinodular goitre, solitary thyroid nodules (cyst, adenoma, malignancy, discrete nodule or multinodular goitre)
183
Thyroid Lumps
| Investigations (5)
TFT + thyroid autoantibodies
CXR + thoracic inlet view: for retrosternal goitres and mets
USS: solid, cystic, complex or part of a group of lumps
Radionuclide scan: hypofunctioning suggests malignancy, hypoerfunctioning suggests adenoma
FNAC
184
Thyroid Lumps
| Complications of Thyroid Surgery (4)
Airway obstruction (haemorrhage/oedema)
Recurrent laryngeal nerve palsy (right > left)
Hyperparathyroidism
Thyroid storm
185
Thyroid Lumps
| Goitre (4)
Aetiology: iodine deficiency, autoimmune, hereditary
Simple, multinodular, diffuse and painless (may have mass effect- dysphagia, stridor, SVC obstruction)
Multinodular usually euthyroid but may be subclinical hyper
186
Thyroid Lumps
| De Quervain's thyroiditis (5)
```
Aetiology: viral URTI, autoimmune
Pathology: thyrotoxicosis --> hypothyroid --> euthyroid
Diffuse painful goitre
Reduced iodine uptake
Self-limiting
```
187
```
Thyroid Lumps
Follicular adenoma (2)
```
Benign solitary thyroid nodules, may cause pressure symptoms
| Do hemithyroidectomy as clinical and diagnostic tests can't tell if benign/malignant
188
Thyroid Cancer
| Aetiology (5)
Papillary (60%): 20-40y/o, node and lung mets
Follicular (25%): 40-60y/o, F>M, haematogenous spread to bone and lungs
Medullary (5%): 1/3 familial (MEN2) and occur in young, can occur sporadically in 40-50y/o
Anaplastic (rare): F>M, >60y/o, rapid growth and aggressive with spread
Lymphoma (5%): F>M, mucosal associated lymphoid tissue (MALT) associated with good prognosis
189
```
Thyroid Cancer
Risk factors (6)
```
```
Solitary thyroid nodule
Solid thyroid nodule
Male
Cold thyroid nodule
MEN2
Radiation exposure
```
190
Thyroid Cancer
| Signs + symptoms (3)
Painless neck mass
Cervical lymphadenopathy
Compression symptoms (dysphagia, stridor, SVC obstruction)
191
Thyroid Cancer
| Investigations (7)
```
TFT
Thyroid autoantibodies
USS neck
CXR
Radionuclide scan
FNAC
Tumour markers: Tg (papillary/follicular), calcitonin (medullary)
```
192
Thyroid Cancer
| Treatment (2)
Thyroidectomy +/- node clearance
| Chemoradiotherapy for lymphoma
193
```
Parathyroid Physiology
Calcium distribution (4)
```
Bone 99%
Intracellular 0.9%
ECF 0.1%
Plasma: 2.2-2.6 (tight limits; plasma conc. takes precedence over bone storage)
194
```
Parathyroid Physiology
Bone cells (3)
```
Osteoblasts: bone building cells that lay down a collagen extracellular matrix which is calcified
Osteocytes: differentiated osteoblasts which regulate osteoblast and osteoclast activity
Osteoclasts: responsible for bone resorption
195
```
Parathyroid Physiology
Vitamin D (1)
```
Converted in the liver then the kidneys to calcitriol (steroid hormone secreted in response to increased PTH)
196
```
Parathyroid Physiology
Calcitriol roles (3)
```
Increased calcium gut absorption
Increased calcium renal reabsorption
Stimulates osteoclasts
197
Parathyroid Physiology
| Functions of calcium (5)
```
Cell signalling
Blood clotting
Apoptosis
Skeletal strength
Regulation of membrane excitability
```
198
Parathyroid Physiology
| Hypocalcaemia (1)
Increased neuronal Na permeability causing hyper excitation and tetany
199
Parathyroid Physiology
| Hypercalcaemia (1)
Reduced neuronal Na permeability, reducing hyperexcitability and depressing neuromuscular activity
200
Parathyroid Physiology
| Definition of parathyroid hormone (1)
Polypeptide hormone produced and released by parathyroid glands in response to reduced free calcium in the plasma
201
Parathyroid Physiology
| Actions of parathyroid hormone (3)
Stimulates osteoclasts to increase calcium and phosphate resorption in bone leading to an increase in the plasma
Inhibits osteoblasts
Increased calcium reabsorption at the kidney tubules and thus decreasing urinary excretion
202
Parathyroid Physiology
| Negative feedback of parathyroid hormone (1)
Increased levels of plasma calcium inhibit PTH causing a shift to greater osteoblast deposition and less osteoclast resorption
203
Parathyroid Physiology
| Definition of calcitriol (1)
Steroid hormone produced by liver and then kidneys from dietary vitamin D in response to increased levels of PTH
204
Parathyroid Physiology
| Actions of calcitriol (4)
Bind to receptors in intestine, bone and kidney
Increased calcium absorption from gut via active transport system
Mobilises calcium stores by stimulating osteoclast activity
Facilitates renal absorption of Ca
205
Parathyroid Physiology
| Calcitonin (3)
Peptide hormone produced by medullary cells in the thyroid gland in response to increased plasma calcium concentration
Binds to osteoclasts to inhibit bone resorption
Increases renal excretion of calcium
206
Hypercalcaemia
| Aetiology (7)
Parathyroid mediated: primary hyperparathyroidism, MEN
Non-parathyroid mediated: malignancy, vitamin D deficiency, sarcoidosis
Medications: thiazide diuretics, lithium
Hyperthyroidism
Acromegaly
Phaeochromocytoma
Adrenal insufficiency
207
Hypercalcaemia
| Signs + symptoms (6)
Bones: pain, osteopenia, osteoporosis, muscle weakness
Stones: renal stones
Neuro: reduced concentration, confusion, fatigue
Cardio: shortening of QT interval, tachycardia, hypertension
Pancreatitis
Features of malignancy eg. lymphadenopathy
208
Hypercalcaemia
| Investigations (4)
Bone profile: increased calcium, albumin, phosphate, vitamin D3, alk phos
Parathyroid hormone: normal/high (inappropriate)- primary hyperparathyroidism, low (appropriate)- malignancy, drug causes
Myeloma screen
ECG: short QT
209
Hypercalcaemia
| Treatment (4)
Rehydration: 0.9% saline 4-6L over 24h with monitoring for fluid overload, consider dialysis for severe renal failure
IV bisphosphonates: after rehydration zolendronic acid over 15 mins
Calcitonin if poor response to bisphosphonates
Parathyroidectomy if acute presentation and severe hypercalcaemia when poor response to other measures
210
Primary Hyperparathyroidism
| Aetiology (3)
Solitary adenoma (80%)
Hyperplasia of all parathyroid glands (20%)
MEN1 (causes parathyroid hyperplasia/adenoma)
211
Primary Hyperparathyroidism
| Pathology (1)
PTH oversecretion causes increased resorption, hypophosphataemia and hypercalcaemia
212
Primary Hyperparathyroidism
| Signs + symptoms (4)
Often asymptomatic with raised Ca on routine tests
Signs related to high Ca: weak, tired, depressed, thirsty, renal stones, abdo pain, pancreatitis and ulcers
Bone resorption effects of PTH can cause pain, fractures and osteopenia/osteoporosis
High BP
213
Primary Hyperparathyroidism
| Investigations (8)
```
High Ca
High PTH (or inappropriately normal)
Low PO4 (unless in renal failure)
High alk phos (from bone activity)
High 24h urine Ca
X-ray: osteosis fibrosa cystica (severe resorption causes sub periosteal erosions, cysts, pepper pot skull)
DEXA: exclude osteoporosis
Abdo ultrasound: renal calculi
```
214
Primary Hyperparathyroidism
| Treatment (2)
Mild: increase fluid intake to prevent stones
| Surgical excision of all 4 glands or the adenoma if high serum/urinary calcium, osteoporosis, renal calculi
215
Secondary Hyperparathyroidism
| Aetiology (3)
Disease outside of the parathyroid glands causes all of the parathyroid glands to become enlarged and hyperactive
Kidney failure
Vitamin D deficiency
216
Secondary Hyperparathyroidism
| Investigations (2)
```
Low Ca
High PTH (appropriately)
```
217
Secondary Hyperparathyroidism
| Treatment (3)
Correct causes
Phosphate binders
Vitamin D
218
Tertiary Hyperparathyroidism
| Aetiology (2)
Occurs after prolonged secondary hyperparathyroidism, causing glands to act autonomously having undergone hyperplastic/adenomatous change
Renal failure
219
Tertiary Hyperparathyroidism
| Investigations (2)
High Ca
| Really high PTH (inappropriately- unlimited by feedback control)
220
Hypocalcaemia
| Aetiology (3)
```
Low PTH (hypoparathyroidism): autoimmune, post-surgical (thyroidectomy/parathyroidectomy)
High PTH (secondary hyperparathyroidism): vit D deficiency, pseudohypoparathyroidism, renal disease
Drugs: bisphosphonates, calcitonin
```
221
Hypocalcaemia
| Signs + symptoms (5)
```
Neuromuscular irritability (tetany): paraesthesia, muscle twitching, Chovstek's sign (facial nerve tapped at masseter muscle = facial muscle on same side contracts momentarily due to nerve hyperexcitability), Trosseau's sign (carpal spasm due to ulnar nerve excitation occurs when sphygmanometer is elevated above systolic pressure)
Prolonged QT
Hypotension
Papilloedema
Extrapyramidal signs, Parkisonism
```
222
Hypocalcaemia
| Investigations (5)
ECG
Low Ca
PTH low/normal (inappropriate): magnesium deficiency or hypoparathyroidism
PTH high (appropriate): renal failure, vit D deficiency, pseudohypoparathyroidism
Magnesium
223
Hypocalcaemia
| Treatment (2)
Mild: oral calcium tablets, calcitriol for vit D deficiency
Severe: IV calcium gluconate
224
Primary Hypoparathyroidism
| Pathology (1)
PTH secretion is reduced due to gland failure, leading to low Ca and high phosphate
225
Primary Hypoparathyroidism
| Signs + symptoms (1)
Hypocalcaemia
226
Primary Hypoparathyroidism
| Investigations (6)
```
Low PTH
Low Ca
High phosphate
Normal alk phos
Normal vit D
ECG: prolonged QT
```
227
Primary Hypoparathyroidism
| Treatment (2)
Calcium supplements
| Calcitriol
228
```
Pseudohypoparathyroidism
Pathology (1)
```
Genetic failure of target cell to respond to PTH
229
```
Pseudohypoparathyroidism
Signs (4)
```
Short metacarpals
Round face
Short stature
Reduced IQ
230
```
Pseudohypoparathyroidism
Investigations (3)
```
Low Ca
High PTH
Normal/high alk phos
231
Pseudopseudohypoparathyroidism (1)
Same as pseudohypoparathyroidism but with normal biochemistry
232
Multiple Endocrine Neoplasia
| Definition (1)
Autosomal dominant functioning hormone producing tumours in multiple organs
233
Multiple Endocrine Neoplasia
| MEN-1 (5)
Tumour suppressor gene
Mutations present 40-60y/o
Parathyroid hyperplasia/adenoma (high Ca)
Pancreas endocrine tumours (eg. insulinoma)
Pituitary prolactinoma or GH secreting tumour (acromegaly)
234
Multiple Endocrine Neoplasia
| MEN-2 (5)
Ret proto-oncogene (tyrosine kinase receptor)
Testing for ret mutations now allows for prophylactic thyroidectomy before neoplasia occurs
Thyroid: medullary thyroid carcinoma
Adrenal: phaeochromocytoma
Hypercalcaemia less common than in MEN-1 but parathyroid hyperplasia does still occur
