Endocrinology Flashcards
Endocrine cells of the pancreas and the hormones they secrete
Beta-cells: insulin and amylin
Alpha-cells: glucagon
Delta-cells: somatostatin
Gamma-cells: polypeptide of unknown function
Definition of hyperosmolar hyperglycaemic state
An acute complication of DM characterised by severe hyperglycaemia with NO ketoacidosis
AKA hyperosmolar non-ketotic state
Precipitants of hyperosmolar hyperglycaemic state
Acute major illness (MI, CVA, sepsis, pancreatitis)
Poor compliance
Dehydration
Clinical features of hyperosmolar hyperglycaemic state
Insidious development, often over several days
- polyuria
- polydipsia
- weight loss
As increases further:
- neuro symptoms (lethargy, focal signs, reduced alertness)
- progress into coma in late stage
NO HYPERVENTILATION OR ABDO PAIN LIKE IN DKA
Definition of ulcer
Break in continuity of the skin penetrating full thickness of dermis
Risk factors for diabetic foot
Diabetic neuropathy Peripheral vascular disease Elderly Deformity Previous history Patient living alone trauma Other microvascular complications (e.g. CKD, retinopathy)
Definition of hammer toe
Fixed deformity with flexion at the PIP joint causing elevation of the PIP joints
Definition of claw toe
Fixed extension at MTP joints + flexion at PIP and DIP joints
Definition of mallet toe
Flexion deformity of DIP joints (often only affects 2nd digit)
Neurovascular examination of diabetic foot
PERFORM AT LEAST 1-2 NEURO and 1-2 VASCULAR TESTS in OSCE
- Monofilament*
- Vibration sense* (128Hz)
- Proprioception*
- ankle reflex
- Pin prick
- Peripheral pulses
- Doppler USS
- ABPI
Wound classifications for diabetic foot
WAGNER GRADES
I: superficial, not infected
II. Deep ulcer +/- tendon involvement, WITHOUT bone involvement
III: Deep ulcer with tendon and bone involvement
IV: Localised gangrene
V: Complete gangrene
Refer to podiatrist for anything grade II and above!
How to test for bone involvement in an ulcer
Probe test - if hits bone = clear path to bone = BONY INVOLVEMENT
Technetium bone scan - good sensitivity, poor specificity
MRI: look for internal involvement (Inx of choice for osteomyelitis)
Foot swab
Methods of reporting ulcer wound
S(AD) SAD: Size (Area, Depth) of ulcer Sepsis - is it infected? Arteriopathy - poor vascular supply? Denervation - neuropathy?
or PEDIS Perfusion: palpable pulsels? Extent: area Depth Infection Sensation
Management of neuropathic ulcers
Control BGL
Smoking cessation
Preparation of wound bed (debridement, treatment of local oedema)
Off-loading = relieving high pressure areas
- Total compact cast/TCC (foot in case, pressure off all critical areas + immobilisation)
- removable casts (strap on and off)
- combination instant cast: removable + POP
Dressing: hydrocolloid, topical silver
Management of foot ingections
Antibiotics: Hospital specific broad spectrum protocols
- augmentin/tazocin ususally
- for soft tissue infections: 1-2 weeks
- for osteomyelitis over 6 weeks
Negative pressure wound healing (Vac dressing)
Hyperbaric oxygen (40x 1h sessions_
Larval therapy (green bottle fly larvae)
Definition of Charcot’s foot
Non-infective, destructive neuropathic arthropathy occurring in a WELL PERFUSED, insensate foot.
Progressive degenerative arthritis resulting from damaged nerves that leads to progressive deterioration of weight bearing joints, usually foot/ankle
Cause of Charcot’s foot
Neurotrauma (due to reduced pain sensation and proprioception) - repetitive mechanical trauma to foot
Neurovascular (dysfunctional blood supply - lax ligaments, microfractures, osteopenia, bone destruction)
Presentation of Charcot’s foot
Atrophic type: "sucked candy cane) Hypertrophic type Rockerbottom foot arch (#s - collapse of tarsal bones - outward bowing of arch) Dislocation/instability of foot osteophytes
Management of Charcot’s foot
Immobilise and offload with total compact cast (TCC)
CROW walker (charcot restraint orthotic walker)
Bespoke shoes with stiffened sole and moulded insoles
Anatomy of anterior pituitary
Sits within sphenoid sella turnica
Cavernous sinus laterally (CN III, IV, V1, V2, VI)
Optic chiasm superiorly
Anterior pituitary develops from oral ectoderm (Rathke’s pouch)
Which hormones does somatostatin inhibit at the anterior pituitary
Thyrotropin releasing hormone
Growth hormone
Evidence of pituitary hormone excess
Acromegaly (GH)
Cushing’s (Cortisol)
Biochemically: IGF-1, prolactin, 24h urinary free cortisol, TSH/Free T4
Evidence of mass effect from pituitary adenomas
Bitemporal hemianopia (optic chiasm) CN lesions (cavernous sinuses)
Pituitary imaging
MRI!
Extensions superiorly to optic chiasm may be discernible
Incidentalomas are quite common - small, non-secreting, do not require treatment
Smaller tumours may be missed (40% of Cushing’s pituitary tumours cannot be seen on imaging)
Symptoms of GH excess (acromegaly)
Overgrowth of soft tissues and cartilage:
- increased ring, shoe and hat size
- enlargement of nose and jaw
- underbite (prognathism)
- increased gap between teeth
- HTN
- increased tongue size
- diabetes mellitus
- mass effects of pituitary
Diagnosis of acromegaly
IGF-1 level (not pulsatile like GH)
Pituitary MRI usually identifies tumour
Causes of acromegaly
Pituitary GH-secreting tumour
Ectopic GHRH secretion
Ectopic GH secretion
Management of acromegaly
Trans-sphenoidal resection of tumour (80% success rate)
Medical treatment:
- Octreotide (long acting somatostatin analogue)
- Dopamine agonists useful in tumours which also secrete prolactin
- RTx for failed surgery
Definition of acromegaly
GH excess AFTER fusion of epiphyses
- overgrowth of soft tissues and cartilage
Definition of gigantism
GH excess BEFORE fusion of epiphyses - large stature and height
Rare (pituitary tumours are rare in childhood)
Cushing’s disease definition
An excess of cortisol in the body secondary to a pituitary adenoma secreting ACTH
Role of dexamethasone suppression test
In ACTH dependent Cushing’s syndrome
Pituitary adenomas secreting ACTH are RELATIVELY resistant to negative feedback by glucocorticoids
Nonpituitary tumours with ectopic ACTH secretion are COMPLETELY resistant to feedback inhibition
i.e. if pituitary dependent, cortisol levels after the dexamethasone suppression will be less than a certain amount (but will be detectable, unlike in healthy patients)
Role of CRH stimulation test in Cushing’s syndrome
45 minutes after IV administration of CRH, most patients with Cushing’s disease will respond with increase in ACTH and cortisol
Those with ectopic ACTH-secreting tumours or adrenal tumours do not respond because pituitary ACTH secretion is already suppressed
Clinical features of hyperprolactinaemia
Premenopausal women: - amenorrhoea - infertility - galactorrhoea - tend to be diagnosed early In men: - hypogonadism - reduced libido - Impotence - often diagnosed late with visual change as symptoms are assumed to be caused by other things In post-menopausal women: - mass effect only (hemianopia, headaches due to raised ICP)
Diagnosis of hyperprolactinaemia
Serum prolactin over 5x normal limit
Management of pituitary prolactinoma
DA-2 receptor agonists:
- bromocriptine, cabergoline
- S/E: nausea, postural hypotension, nasal stuffiness
Management of secondary hyperthyroidism (i.e. excess TSH secretion from pituitary)
Surgery
Radiotherapy
OR octreotide (somatostatin analogue)
Which are the most common of pituitary adenomas
- non-functioning/gonadotropin secreting tumours
- Prolactin secreting tumours (commonest FUNCTIONING tumour)
- GH secreting
- Cushing’s (ACTH secreting)
- TSH secreting tumours can occur but are rare
Causes of hypopituitarism
Most commonly due to pituitary tumour Past pitutiary Sx or Rtx (50% develop within 4y) Autoimmune disease Postpartum lymphocytic hypophysitis Haemochromatosis Sheehan's syndrome (following PPH) Carniopharyngioma Rare genetic causes
Clinical features of hypopituitarism
ACTH/cortisol: hypotension, weight loss, fatigue
TSH: cold intolerance, fatigue
Gonadotropins: loss of menses, libido and shaving
Prolactin: no clinical effects
GH: subtle reduction in exercise tolerance, body composition and metabolism (growth failure in children)
Management of hypopituitarism
Only TSH and ACTH are essential for life
Replace cortisol: e.g. 20-30mg hydrocortisone/day
Replace thyroid - monitor with serum free T4 (aim for normal range)
Replace sex steroids (OCP or HRT, testosterone via 3 monthly IM injection or daily cutaneous gel)
Replace gonadotropins for fertility
No need to replace prolactin, GH replacement only given in children with growth failure
Hormones secreted from posterior pituitary
Vasopressin/ADH (water balance)
Oxytocin (suckling reflex)
Causes of posterior pituitary disease
Due to posterior pituitary or hypothalamic disease (usually hypothalamic)
Tumour or trauma most common
Management of central DI
Long-term treatment with desmopressin
Zones of the adrenal gland
Cortex (90% - mesodermal origin - steroid hormones)
Zona glomerulosa: mineralocorticoids (aldosterone) - retains salt
Zona fasciculata: glucocorticoids (cortisol)
Zona reticularis: androgen/sex hormones (DHEA - testosterone, oestrogen)
Medulla (10% - derived from neural crest cells - catecholamines)
- Adrenaline
- Noradrenaline
- Dopamine
Exogenous glucocorticoids required per day to replace all lost cortisol if there is NO endogenous production
Prednisolone: 5mg/day
Hydrocortisone 30mg/day
Cortisone acetate 37.5mg/day
Dexamethasone 0.5-1mg/day
Which glucocorticoid medication is biochemically identical to endogenous cortisone
Hydrocortisone
Doses of exogenous corticosteroids at which suppression of HPA axis is likely to occur
Over 10mg/day prednisolone for over one month
(1.5-2x replacement dose)
i.e. unlikely to occur following short courses for asthma etc,
Almost certainly will occur for temporal arteritis, transplant rejection treatment etc
Definition of phaeochromocytoma
Tumour arrising from chromaffin cells in the sympathetic nervous system (usually in the adrenal medulla) that secrete any combination of adrenaline and/or noradrenaline and occasionally dopamine
Clinical features of phaeochromocytoma
Episodic/paroxysmal in 50% - HTN - headaches - sweating - anxiety/fear - nausea, vomiting - chest, abdo pain Between episodes (not experienced by all patients) - cold hands/feet - weight loss - hyperglycaemia or hypo - postural hypotension
Genetic syndrome associated with phaeochromocytoma
MEN2
Investigations in phaeochromocytoma
Elevated catecholamines in blood and urine (3-4x upper limit of normal at LEAST)
Plasma free metanephrines (metabolites of adrenaline)
Clonidine suppression test if equivocal results
CT/MRI of adrenals
Management of phaeochromocytoma
Alpha blockade (pehoxybenzamine) Beta blockade (atenolol or metoprolol) Once stable after 1-2 weeks - surgical removal
Embryological origin of the thyroid gland
Develops from pharyngeal floor (1st and 2nd pharyngeal pouches) in the 3rd week of gestation
Cells of the thyroid gland
Follicular cells: secrete thyroid hormone (mainly T4/thyroxine)
Follicles filled with colloid stores thyroid hormone
Parafollicular cells: secrete calcitonin (only significant in times of high calcium demand i.e. breastfeeding, pregnancy)
Thyroid hormone ratios, carriage etc.
93% T4/thyroxine
- mostly converted to T3 in tissues
- higher binding protein affinity (10x half-life of T3)
7% T3/triiodothyronin
- 4x as potent as T4 (higher affinity for receptors)
Over 99% is protein-bound in plasma (thyroxine-binding globulin, albumin)
Actions of thyroid hormone
Metabolic rate and metabolism: - inc. heat production - inc. O2 consumption - inc. lipolysis - inc. glycogenolysis Cardiovascular - inc. contractility - inc. cardiac output Sympathetic effects: - inc. beta receptors - inc. catecholamine permissive actions - red. a receptors Gastrointestinal: - inc. gut motility Growth effects: - permissive for GH synthesis, secretion and action - important in development of CNS
Most common cause for hypothyroidism worldwide
Iodine deficiency
Most common cause for hypothyroidism in iodine-sufficient areas
Hashimoto’s thyroiditis
Aetiology of hypothyroidism
- Primary: thyroid failure (90%)
- Hashimoto’s
- Iatrogenic (Li, RTx, Tx for hyperthyroid)
- Infiltrative (amyloid)
- Iodine deficiency
- Congenital - Secondary: pituitary deficit of TSH
- adenomas or destruction - Tertiary: hypothalamic deficit of TRH
- rare, also adenomas/destruction - Peripheral resistance to hormone
Clinical features of hypothyroidism
Psych: mental sluggishness, psychosis, confusion
Eyes: puffy
ENT: deafness, hoarseness
Skin: dry, alopecia
Rheum: myalgia, arthralgia, proximal myopathy
Heart: HF, hypotension, bradycardia
GIT: constipation
Metabolic: intolerance to cold, weight gain, red. appetite
GYN: menorrhagia
Haem: anaemia
Neuro: coma, carpal tunnel
Definition of myxoedema coma
A rare life-threatening complication of hypothyroidism characterised by profound lethargy or coma, and usually accompanied by hypothermia
Cause of myxoedema coma
Decompensation of hypothyroidism from:
- sepsis
- exposure to cold
- CNS depressants (sedatives, narcotics, antidepressants)
- trauma/surgery
- stroke, CHF, burns
- intravascular volume contractions
Management of myxoedema coma
Reduce further heat loss ICU monitoring Support respiration as indicated IV hydration IV thyroxine Glucocorticoids (until adrenal insufficiency excluded) Treat precipitating factors
Definition of Hashimoto’s thyroiditis
A chronic autoimmune mediated destruction of the thyroid gland, characterised by gradual thyroid failure due to apoptosis of thyroid epithelial cells
Diagnosis of Hashimoto’s thyroiditis
Raised autoantibodies: - thyroglobulin antibodies (TgAb) - thyroid peroxidase antibodies (TPO) - TSH receptor inhibiting antibodies Iodine N Thyroid imaging: - reduced uptake on radioactive iotine uptake scan
Types of diabetes medications
Biguanides (metformin) Sulfonylureas (glicazide) Thiazolidinediones (pioglitazone) Alpha-glucosidase inhibitor (acarbose) Insulin analogues
Biguanides: example, mechanism
Metformin
Sensitises peripiheral tissues to insulin
+
Stimulatino of hepatic AMPK - reduced hepatic glucose production
Side effects of metformin
GI upset
Lactic acidosis
Anorexia
Contraindications to metformin
Liver dysfunction (or alcohol abuse) Renal dysfunction (GFR 30ml/min) Cardiac dysfunction
Mechanism of sulfonylureas
Glicazide
Blocks K+ channel - depolarisation of beta cells - calcium influx - insulin release
Side effects and contraindications of sulfonylureas (glicazide)
Hypoglycaemia
weight gain
Contraindicated in severe liver dyfunction
Do not combine with a non-sulfonylurea or pre-prandial insulin
Mechanism of pioglitazone
Inc. peripheral insulin sensitivity from reducing FFA release from adipose
Side effects of pioglitazone
Heart failure
Oedema
Increased fracture risk
Increase bladder cancer
Contraindications to piioglitazone
Class II or higher congestive heart failure
DO NOT COMBINE WITH INSULIN
Mechanism of acarbose
Inhibits brush border alpha- glucosidase - reduced GI absorption of carbohydrates
Indication for acarbose
Postprandial hyperglycaemia
Side effects of acarbose
Flatulence
Abdominal cramps
Diarrhoea
Contraindications of acarbose
Inflammatory bowel disease
Severe liver dysfunction
Anti-thyroid medications
Carbimazole: inhibits iodine and TPO interactions with thyroglobulin
Propylthiouracil reduced T4 to T3 conversion in addition to above mechanism
Side effects of anti-thyroid medications
Nausea/vomiting Rash hepatitis Cholestasis Agranulocytosis
Contraindications to anti-thyroid medications
renal and liver disease
Carbimazole: 1st trimester pregnancy
Propythiouracil: 2nd and 3rd trimester pregnancy
Recommended 1st and 2nd line oral hypoglycaemic agents
1st: Metformin
2nd: sulfonylureas/DPP-4 inhibitors
Which oral hypoglycaemic agent has the highest risk of hypoglycaemic episodes
Sulfonylureas
Which oral hypoglycaemic agents have the lowest cost?
Metformin and sulfonylureas
Which oral hypoglycaemic agents cause weight loss?
Incretins (exenatide), gliflozins
Diabetic medications which cause weight gain:
Insulin, sulfonylureas, glitazone
Initial type 2 diabetes management according to HbA1c
less than 7.5: lifestyle modification + metformin - follow up in 3 months
7.5 - 9%: metformin + SU/DDP-4i/insulin
Greater than 9% (OR symptomatic hyperglycaemia) - concern about relative insulin deficiency therefore start insulin immediately (+metformin)
Mechanism of DDP-4 inhibitors
DDP-4 is an enzyme which cleaves endogenous GLP-1 so that is has a very short half-life. Therefore by inhibiting this enzyme, inhibit cleavage, increases half-life of GLP-1 (increases secretion of insulin, inhibits secretion of glucagon)
Which oral hypoglycaemic agent has the least side effect profile
DDP-4 inhibitors (gliptins)
Example of DDP-4 inhibitor
Gliptins e.g. sitagliptin
Mechanism of GLP-1 agonists
Binds to GLP-1 receptor, therefore does not rely on endogenous GLP-1 (more efficacious than DDP-4 inhibitors)
Side effects of GLP-1 agonists
Red. gastric emptying (early satiety, red. appetite, nausea in 50%[usually improves]) Weight loss (more than SGLT2-i) - 1/3 over 5% weight loss - 1/3 less than 5% - 1/3 no effect on weight
Long term use - down regulation of receptors - reduced efficacy over time
Example of a GLP-1 agonist
Exenatide
Mechanism of SGLT-2 inhibitor
Inhibits co-transport of Na/glucose in PCT of nephron - inhibits reabsorption of glucose in PCT - reduced tubular renal threshold for glycosuria - glycosuria at lower glucose concentration
Side effects of SGLT-2 inhibitors
Weight loss
Genital infections, UTIs
Polyuria
Volume depletion, reduced blood pressure
Contraindications for SGLT-2 inhibitors
GFR less than 60
Not toxic, just requires a working nephron to exert effect
Example of a SGLT-2 inhibitor
Gliflozins (dapagliflozin)
