Obesity Flashcards
What clinical features point towards a Cushing’s diagnosis?
- Recent rapid weight gain
- Tuncal or central obesity
- Fullness of face or “moon face”
- Increased blood pressure
- Glycosuria (associated with insulin resistance)
What are the clinical features of Cushing’s syndrome?
- Osteoporosis
- CVD (HTN, cardiomyopathy, atherosclerosis)
- Dyslipidemia
- Diabetes
- Obesity
- GH/GF1 axis impairment
- Myopathy
- Gonadal axis impairment
- Infections
- Peptic ulcer
- Nephrolithiasis
- Skin manifestations
- Cataracts, glaucoma
- Neuropsychiatric disorders
- Thrombophilia
What are the BMI weight classes?
Different weight classes are defined based on a person’s body mass index (BMI) as follows:
healthy weight: 18.5–24.9 kg/m2 overweight: 25–29.9 kg/m2 obesity I: 30–34.9 kg/m2 obesity II: 35–39.9 kg/m2 obesity III: 40 kg/m2 or more.
When do adults need to be referred to tier 3 care for obesity?
- the underlying causes of being overweight or obese need to be assessed
- the person has complex disease states or needs that cannot be managed adequately in tier 2 (for example, the additional support needs of people with learning disabilities)
- conventional treatment has been unsuccessful
- drug treatment is being considered for a person with a BMI of more than 50 kg/m2
- specialist interventions (such as a very-low-calorie diet) may be needed
- surgery is being considered.
Which group of patients should be considered for bariatric surgery?
Bariatric surgery is a treatment option for people with obesity if all of the following criteria are fulfilled:
- They have a BMI of 40 kg/m2 or more, or between 35 kg/m2and 40 kg/m2 and other significant disease (for example, type 2 diabetes or high blood pressure) that could be improved if they lost weight.
- All appropriate non-surgical measures have been tried but the person has not achieved or maintained adequate, clinically beneficial weight loss.
- The person has been receiving or will receive intensive management in a tier 3 service
- The person is generally fit for anaesthesia and surgery.
- The person commits to the need for long-term follow-up.
What is the dexamethasone suppression test? What is its use in clinical practice?
Dexamethasone is an exogeneous steroid that will cause suppression of the pituitary through negative feedback. It is used to assess the integrity of the hypothalamo-pituitary-adrenal axis. Dexamethasone binds to glucocorticoid receptors in the pituitary and thereby inhibits ACTH secretion by the pituitary gland. When testing the adrenal functions in patients with Cushings syndrome, Dexamethasone may be administered in low (1–2 mg) and/or high (8 mg) doses.
Low dose dexamethasone suppresses cortisol production in normal subjects. High dose dexamethasone suppresses steroid production in pituitary dependant Cushings syndrome - or Cushing’s disease. It will not reduce steroid production in patients with primary adrenal tumours or in those with ectopic ACTH production.
Normal subject: Reduction in cortisol levels following low-dose dexamethasone.
Cushing’s disease: No reduction in cortisol output after low-dose dexamethasone, but inhibition of cortisol output following high-dose dexamethasone.
Adrenal tumour or ectopic ACTH: No reduction in steroid production after low or high dose dexamethasone
In patients with high resting cortisol and ACTH levels, but with the ACTH levels being not suppressed with low or high dose Dexamethasone, ectopic ACTH secretion should be considered
What structure is anterior to the pituitary gland and can be affected in pituitary adenoma?
Optic nerve chiasm
What is bitemporal hemianopia?
A type of partial blindness where vision is missing in the outer half of both the right and left visual field. It is usually associated with lesions of the optic chiasm, the area where the optic nerves from the right and left eyes cross near the pituitary gland.
What pituitary tumours can occur?
- Non-functional adenomas
- Most common type
- Typically asymptomatic until very large in size
- Then experience headache, vision problems as it compresses on the optic chiasm - Prolactinomas
- Benign
- Increased secretion of prolactin: irregular periods, amennorhia, breastmilk production, erectile dysfunction, decreased libido, enlarged breasts, low sperm count, less body hair - ACTH-producing tumours
- Cushing’s Disease: fat buildup in face, neck, back, belly, chest; Arms + legs become thin; purple stretch marks; HTN
- Weakening of bones - Growth Hormone-producing tumours
- Acromegaly: extra growth in skull/hands/feet, deepened voice, change in facial appearance, wide spacing of teeth, joint pain, snoring/sleep apnea, diabetes
What is the effect of metyrapone?
Metyrapone is a pyridine derivative and a glucocorticoid synthesis inhibitor.
Metyrapone inhibits 11-beta-hydroxylase, thereby inhibiting synthesis of cortisol from 11-deoxycortisol and corticosterone from desoxycorticosterone in the adrenal gland.
What is the recommended test for adrenal function?
The recommended initial diagnostic tool to determine adrenal insufficiency (and gold standard for diagnosing primary adrenal insufficiency) is the short corticotropin test (also called ACTH stimulation test) with cortisol response measurements at 0, 30, and/or 60 minutes.
What are the biochemical abnormalities in Cushing’s other than cortisol levels?
Hypokalemia and hypernatremia
What 3 arteries supply the adrenal gland? Venous drainage?
- Superior suprarenal artery arising from the inferior phrenic artery
- Middle suprarenal artery arising directly from the abdominal aorta
- Inferior suprarenal artery arising from the renal artery
Venous blood is drained via the suprarenal veins with the right suprarenal vein draining into the inferior vena cava and the left suprarenal vein draining into the left renal vein.
As a result of the adrenal gland’s rich blood supply what is there a risk of?
The adrenal glands have a very rich blood supply and this accounts for the frequent metastasis of malignancies – such as lung cancer, to the adrenal gland.
In spite of this very rich blood supply, ischaemic necrosis of adrenals following prolonged circulatory shock – particularly in patients who have had severe post-partum haemorrhage, is a very well recognised clinical entity.
What functions do the cells in the zona glomerulosa, zona fasciculata and zona reticularis perform?
Zona glomerulosa: mineralocorticoids (aldosterone)
Zona fasciculata: glucocorticoids (cortisol + androgens)
Zona reticularis: androgens (DHEA)
Inner medulla: Chromaffin cells secrete catecholamines, adrenaline and noradrenaline.
How can primary adrenal tumours manifest?
- Glucocorticoid excess (Cushings syndrome)
- Mineralocortiocoid excess (Conn’s syndrome)
- Androgen excess
What are the tumours that arise from the adrenal medulla called?
Pheochromocytoma
Adrenal adenoma/carcinoma
What are the risks of long-term steroid use?
- osteoporosis (fragile bones)
- hypertension (high blood pressure)
- diabetes
- weight gain
- increased vulnerability to infection
- cataracts and glaucoma (eye disorders)
- thinning of the skin
- bruising easily
What are the causes of Cushing’s disease?
- Iatrogenic (steroid use)
- Primary ACTH
- Ectopic ACTH
- Primary adrenal tumour (ACTH independent)
Describe Cushing’s Disease
- Female:Male 3:1
- Age 25-45
- 70% of Cushing’s have pituitary ACTH producing adenoma
How do you confirm cortisol excess?
- Plasma cortisol (diurnal variation in secretion; stress responsive; sleeping cortisol levels are usually undetectable)
- Salivary cortisol
- Urinary free cortisol (urine sample)
- Dynamic tests (Overnight Dexamethasone suppression test; 2D Low Dose Dexamethasone suppression test) - Gold standard!
What other conditions/treatment can cause an increase/decrease in cortisol levels?
Raised in:
- Pregnancy
- OCP
- Suppressed in illness
What is the diagnosis from combined tests for adrenal function?
High dose Dexamethasone + CRH
Both negative = ectopic
Either positive = pituitary
What is an adrenal crisis? What is the treatment?
Sick patient, hypotension, hyponatremia
- Check random serum cortisol + ACTH levels
Treat with high dose replacement IV hydrocortisone (100mg every 6h) \+ IV saline (2-3L first hour, 3-4L/day)
What is the treatment of adrenal insufficiency?
In primary adrenal disease: replace aldosterone + cortisol
In pituitary disease: replace cortisol (aldosterone secretion is regulated by K+ and angiotensin II, not pituitary ACTH)
Cortisol/hydrocortisone can be given 1-3x/day
- Slightly larger dose when waking and 2 lower doses during the day (i.e. 10mg, 5mg, 5mg)
Add longer acting steroids = 1/day
- Prednisolone 2.5-7.5mg
- Dexamethasone 0.25-0.75mg
Single dose at night/on waking
What are signs of under replacement of glucocorticoids? Over replacement?
Under replacement:
- Weight loss
- Hyponatremia
- Increased pigmentation
Over replacement:
- Cushing’s syndrome (obesity, striae, HTN, hyperglycaemia)
- Changes in bone turnover/osteoporosis
When is hydrocortisone typically measured?
Morning
- Looking for abnormal urinary free cortisol levels
- Increased variability of cortisol levels
Which hormones are released from the anterior pituitary? Posterior pituitary?
Anterior:
- TSH
- GH
- ACTH
- FSH/LH
- Prolactin
- Endorphins
Posterior:
- Oxytocin
- ADH -> Acts on the collecting ducts of the kidney to increase the number of aquaporin channels allowing water to be absorbed in the blood
What is Diabetes Insipidus?
This is a rare condition.
This is where either too little vasopressin is produced by the pituitary – ‘cranial diabetes insipidus’ or the kidney becomes insensitive to vasopressin and does not make aquaporin channels and reabsorb water from the collecting ducts – ‘nephrogenic diabetes insipidus’.
In these conditions large quantities of dilute urine are produced – polyuria – and to compensate people drink large quantities of water – polydipsia.
If people are unable to drink water they will develop high body sodium levels, hypernatraemia, and become dehydrated. This is the basis of the water restriction test to diagnose diabetes insipidus.
What is the SIADH secretion?
This syndrome is much more common. Many stimuli can override osmolality control and cause the release of inappropriately high amounts of ADH which causes reabsorbtion of water from collecting ducts and causes urine to have high sodium content or osmolality while serum sodium levels drop (hyponatraemia) as water is retained.
Diagnosis is made by checking paired serum osmolality and urine osmolality and finding serum osmolality is low whilst urine osmolality is high.
What are the causes of SIADH?
- Lung diseases – cancer, pneumonia
- Brain lesions – tumour, head injury and bleed, stroke
- Drugs – e.g. carbamazipine, selective serotonin reuptake inhibitors (SSRIs)
- Miscellaneous causes
What is the clinical approach to hyponatremia?
Exclude pseudohyponatraemia which is caused by a laboratory error if there are high levels of serum glucose, lipids, protein or urea. The serum osmolality will be normal.
If true hyponatreamia:
Symptoms: Headache, nausea and dizziness. If severe can result in coma.
Signs – Check the hydration status of the patient
Dehydrated / Hypovolaemic (increased urinary Na > 20mmol):
Cool peripheries / prolonged capillary refill Tachycardia / can be weak, thread pulse Postural hypotension Confusion Dry mucous membranes Reduced skin turgor
Fluid Overloaded / Hypervolaemia (oedematous patient):
Tachycardia / bounding pulse Raised JVP Pulmonary oedema or pleural effusions Ascites Peripheral oedema Once you have decided hydration status you can measure urinary sodium and osmolality in addition to help reach a diagnosis.
What is the clinical approach to hypernatremia?
This is more unusual and is really only seen associated with dehydration where the person has been unable to access water.
This usually occurs in elderly patients who have dementia which has impaired their sense of thirst or patients in medically induced comas on ITU. It can also occur if you are in a hot weather (e.g. a desert) and do not have enough water.
What is metyrapone? Which enzyme does it block?
Cortisol synthesis inhibitor to reduce his adrenal steroid output
11 B-hydroxylase
What tests can be used in screening for Cushing’s?
- Low dose (1mg) overnight dexamethasone suppression test
- Urinary free cortisol
- 48h low dose dexamethasone suppression test
- Late-night salivary cortisol
Which test can differentiate between Pituitary and Adrenal Cushing’s?
Plasma ACTH levels
Following positive initial screening for Cushing’s, what test would be performed If ACTH is raised?
Pituitary imaging
Following positive initial screening for Cushing’s what test would be performed If ACTH is not raised?
Adrenal imaging
Which test would allow discrimination between a pituitary and ectopic source of excess ACTH?
Inferior petrosal sinus sampling
What would be the most useful first line investigation if ectopic ACTH excess was suspected?
Chest xray
Which electrolyte abnormality can be seen in Cushing’s?
High sodium, low potassium, high bicarbonate
A 45-year-old man presents to his GP for a review of his orlistat treatment for obesity. He has been taking orlistat 120mg immediately before each meal.
It is 12 weeks since he began treatment. His weight prior to starting treatment was 124kg. He is weighed today and found to be 119kg.
His liver and renal function are within the normal range.
What is the most appropriate decision option with regard to continuing the orlistat treatment?
Stop immediately + consider other weight loss strategies
If a patient has not lost at least 5% body weight within 12 weeks of starting orlistat, then the treatment must be stopped.
Practice prescribing a regular lipase inhibitor to help with weight loss, from the list provided. The patient has no known drug allergies. The time is 8am.
Orlistat, 120mg, PO
What is the most adequate primary test for Cushing’s?
- Overnight dexamethasone suppression (1mg at 11pm + 9am cortisol; < 50 = negative)
- 24h urine collection of cortisol
What is Prader-Willi syndrome?
A genetic condition causing overfeeding -> obesity, no puberty
- Damage to chromosome 15
- Paternal inheritance
Angel-Man syndrome = the same but of maternal inheritance
What is the screening for cortisol levels?
- Loss of circadian rhythm
- Midnight cortisol (saliva) - Lack of normal feedback suppression
- Overnight dexamethasone suppression
- Low dose dexamethasone suppression - 24h urinary cortisol
How can you distinguish between pituitary adenoma, adrenal adenoma, an ectopic, or steroid use causing Cushing’s?
Pituitary Adenoma:
- Increased overnight dexamethasone
- Increased low dose dexamethasone
- DECREASED high dose dexamethasone
- Increased ACTH
Adrenal Adenoma:
- Increased overnight dexamethasone
- Increased low dose dexamethasone
- Increased high dose dexamethasone
- DECREASED ACTH
Ectopic:
- Increased overnight dexamethasone
- Increased low dose dexamethasone
- Increased high dose dexamethasone
- Increased ACTH
Steroids:
- Increased overnight dexamethasone
- Increased low dose dexamethasone
- Increased high dose dexamethasone
- DECREASED ACTH
What is the typical treatment for acne?
Topical benzylperoxidase
Doxycycline
Vitamin A derived compounds
What is the treatment for Addison’s Crisis/adrenal crisis?
Give hydrocortisone IV to raise BP. Also get blood cortisol levels to determine if it’s Addison’s disease
What is Pickwickian syndrome?
- Obstructive sleep apnea
Complication of obesity b/c of decreased muscle tone when sleeping + obstructing airways (loud snoring + shallow breathing) - Excessive daytime somnolence
What is Sheehan’s syndrome?
Post-partum hemorrhage -> pituitary infarct of the hypophyseal artery
- Tiredness, no breast feeding (estrogen, progesterone, prolactin, oxytocin)
What is Nelson’s syndrome?
In bilateral adrenelectomy b/c of no feedback to pituitary gland = increased size of pituitary cells = pituitary adenoma + hyperpigmentation b/c of increased ACTH (also in Addison’s)
- MSH -> stimulates melanocytes to produce melanin
What is the effect of vasopressin? Aldosterone?
Vasopressin/ADH = H2O retention
Aldosterone = Salt retention
What is the treatment for adrenal crises?
- Saline
- Steroids
- Salt
- Sugar
Why do you get proximal myopathy in Cushing’s disease?
11-B HSD enzyme can inactivate steroid activity in certain areas (deactivates cortisol) -> why fat is around trunk + face and there is proximal myopathy and thin arms/legs
What is vitiligo?
Autoimmune attack on melanocytes
What is the steroid dose in adrenal crisis?
100mg hydrocortisone i.v. or i.m. followed by rapid rehydration with i.v. administration of 0.9% saline solution (or equivalent).
Please maintain the patient on hydrocortisone at a dose of 200mg hydrocortisone per 24 hours (preferably by continuous i.v. infusion, alternatively by i.v. or i.m. injection of 50mg hydrocortisone every 6 hours) until clinical recovery and further guidance by an endocrinologist.
How is Addison’s diagnosed?
Elevated 9am cortisol levels + synthACTHen
