Endocrinology Flashcards
Describe thyroid cancer?
A. Papillary carcinoma
Usually contain a mixture of papillary and colloidal filled follicles. Histologically tumour has papillary projections and pale empty nuclei. Seldom encapsulated. Lymph node metastasis predominate Haematogenous metastasis rare.
B. Follicular adenoma
Usually present as a solitary thyroid nodule. Malignancy can only be excluded on formal histological assessment
C. Follicular carcinoma
May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
Vascular invasion predominates
Multifocal disease raree
D. Medullary carcinoma
C cells derived from neural crest and not thyroid tissue. Serum calcitonin levels often raised
Familial genetic disease accounts for up to 20% cases
Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
E. Anaplastic carcinoma
Most common in elderly females
Local invasion is a common feature. Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
what is the management of acromegaly?
- Trans-sphenoidal surgery is the first-line
If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
a. somatostatin analogue
directly inhibits the release of growth hormone. for example octreotide
effective in 50-70% of patients
b. pegvisomant
GH receptor antagonist - prevents dimerization of the GH receptor
once daily s/c administration
very effective - decreases IGF-1 levels in 90% of patients to normal
doesn’t reduce tumour volume therefore surgery still needed if mass effect
c. dopamine agonists: bromocriptine
the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
effective only in a minority of patients
Describe sulfonylureas.
They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.
Common adverse effects
1. hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
2. weight gain
Rarer adverse effects
1. hyponatraemia secondary to syndrome of inappropriate ADH secretion
2. bone marrow suppression
3. hepatotoxicity (typically cholestatic)
4. peripheral neuropathy
Sulfonylureas should be avoided in breastfeeding and pregnancy.
Which Medications that can cause false negative renin:aldosterone ratio?
- Angiotensin-converting enzyme inhibitors (e.g. ramipril or lisinopril).
- Angiotensin receptor blockers (e.g. losartan).
- Direct renin inhibitors (e.g aliskiren).
- Aldosterone antagonists (e.g. spironolactone or eplerenone).
what are the causes of primary hyperaldosteronism?
- bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases.
- adrenal adenoma: 20-30% of cases (Conn’s syndrome)
- unilateral hyperplasia
- familial hyperaldosteronism
- adrenal carcinoma
features of primary hyperaldosteronism?
- hypertension
increasingly recognised but still underdiagnosed cause of hypertension - hypokalaemia
e.g. muscle weakness
this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients, and is more common with adrenal adenomas - metabolic alkalosis
- Nocturnal hypertension
- Incidental adrenal mass
- Resistant oedema
7.Asymptomatic Patients
What are the investigation used for primary hyperaldosteronism?
Patients should be screened for primary hyperaldosteronism, e.g.
1. hypertension with hypokalemia
2. treatment-resistant hypertension
Investigations:
1. plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
should show
↑ aldosterone and ↓renin levels (negative feedback due to sodium retention from aldosterone)
- following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
- if the CT is normal adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia
What is the management of primary hyperaldosteronism?
- adrenal adenoma: surgery (laparoscopic adrenalectomy)
- bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
how to differentiate between primary and secondary hyperaldosteronism
Secondary Hyperaldosteronism
Unlike primary hyperaldosteronism which is caused by the autonomous overproduction of aldosterone, secondary hyperaldosteronism results from an appropriate physiological response to stimuli such as renin.
Clinically, both conditions present with hypertension and hypokalaemia.
Patients with secondary hyperaldosteronism often demonstrate signs of volume overload such as oedema or ascites.
The ↑ plasma renin activity (PRA) level is a distinguishing factor. ↑ aldosterone level
What are the causes of primary hyperparathyroidism?
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma
What is the differential diagnosis of hyperparathyroidism?
- Familial Hypocalciuric Hypercalcaemia (FHH) : ↓ urinary urinary calcium excretion. Thus, a
24-hour urine ca measurement can be instrumental in differentiating between this and primary hyperparathyroidism. - Malignancy-Associated Hypercalcaemia : arise from local osteolytic activity or systemic factors such as tumour production of parathyroid hormone-related protein (PTHrP).
similar biochemical profiles to primary hyperparathyroidism.
The presence of symptoms such as weight loss, fatigue and anorexia may suggest malignancy over primary hyperparathyroidism which tends to be asymptomatic or presents with non-specific symptoms like polyuria and constipation.
↓ PTH levels in malignancy-associated hypercalcaemia compared to ↑ in primary hyperparathyroidism.
- Secondary Hyperparathyroidism:
This results from increased PTH secretion in response to ↓ca and/or ↑phosphataemia.
Common causes include CKD and vitamin D deficiency.
These conditions can be differentiated from primary hyperparathyroidism by the presence of ↓ ca, ↑ phosphate levels or ↓ GFR in secondary hyperparathyroidism.
What is the management of primary hyperparathyroidism?
The 2019 NICE guidelines recommend parathyroidectomy for most patients with diagnosed primary hyperparathyroidism due to the high cure rates (up to 98%) and reduced risk of drug side effects.
Surgery is indicated for those with one or more of:
1. Symptomatic disease
2. Symptoms of hypercalcaemia
3. Osteoporosis and/or fragility fractures, Renal stones or nephrocalcinosis
4. Age <50 years
5. Serum adjusted ca of 2.85 mmol/L or above
6. Estimated eGFR of > 60 mL/min/1.73 m²
When parathyroid surgery is not acceptable, NICE recommends specialist management of hypercalcaemia with either:
- Calcitonin which reduces serum calcium concentrations by inhibiting bone and kidney resorption of calcium
- Cinacalcet which is a calcimimetic and acts to reduce serum calcium concentrations while not affecting bone density or urinary calcium concentrations
- Desunomab which also impairs calcium resorption
- Bisphosphonates
what investigation should be done for primary hyperparathyroidism?
- bloods
↑ calcium,↓ phosphate
PTH may be ↑ or (inappropriately, given the ↑calcium) normal - technetium-MIBI subtraction scan
- x-ray findings
pepperpot skull
osteitis fibrosa cystica
What is Familial hypercholesterolaemia (FH)?
autosomal dominant condition. classified as defects in the LDL receptor (most common), apolipoprotein B (ApoB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9).
When we should suspect Familial hypercholesterolaemia FH?
NICE suggest that we should suspect FH as a possible diagnosis in adults with:
1. a total cholesterol level greater than 7.5 mmol/l and/or
- a personal or family history of premature coronary heart disease (an event before 60 years in an index individual or first-degree relative)
children of affected parents:
1. if one parent is affected by familial hypercholesterolaemia, arrange testing in children by age 10
2. if both parents are affected by familial hypercholesterolaemia, arrange testing in children by age 5
How is Familial hypercholesterolaemia diagnosed?
Clinical diagnosis is now based on the Simon Broome criteria:
1. in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus:
2. for definite FH: tendon xanthoma (Achilles tendon importantly) in patients or 1st or 2nd degree relatives or DNA-based evidence of FH
- for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels
What is the action of evolocumab in Familial hypercholesterolaemia ?
Evolocumab prevents PCSK9-mediated LDL receptor degradation. Evolocumab binds selectively to PCSK9 and prevents circulating PCSK9 from binding to the low-density lipoprotein receptor (LDLR) on the liver cell surface, resulting in reduced LDL-cholesterol.
Use of evolocumab is associated with a reduction in levels of free PCSK9 and this is taken as a measure of target engagement. it lowers LDL cholesterol by more than 50% in 85% of patients who are treated.
what is the mechanism of action of Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)?
- DPP-4 inhibitors ↑ levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
- oral preparation
- trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
- do not cause weight gain
NICE guidelines on DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems
a thiazolidinedione is contraindicated or
the person has had a poor response to a thiazolidinedione
How does orlistat works?
by inhibiting gastric and pancreatic lipase to reduce the digestion of fat
Can you classify BMI?
Underweight < 18.49
Normal 18.5 - 25
Overweight 25 - 30
Obese class 1 30 - 35
Obese class 2 35 - 40
Obese class 3 > 40
What are Na levels?
mild: 130-134 mmol/L
moderate: 120-129 mmol/L
severe: < 120 mmol/L
How to treat acute (<48hypernatremia?
Hypertonic saline is normally the first-line treatment in severe hyponatremia and should be initiated in a high-dependency unit.
Normally a bolus of 150ml of 3% sodium chloride is used with repeat blood tests performed 30 minutes after the first bolus.
A 2nd bolus can be performed if an increase of 5mmol/L of sodium is not achieved.
Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
what is Osmotic demyelination syndrome (central pontine myelinolysis)?
can occur due to over-correction of severe hyponatremia
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema.
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
what MODY and its classification?
monogenic diabetes, typically autosomal dominant inheritance pattern.
HNFA = hepatocyte nuclear factor
GCK = glucokinase
MODY1 (HNF4A) (rare cause of monogenic diabetes)
MODY2 (GCK mutation)– 20% MODY3 (HNF1A mutation) – 60%
MODY4 (PDX1 or insulin gene promoter factor 1)
MODY5 (HNF1B), and so on.
What is pentagastrin stimulation test?
assesses the production of calcitonin by parafollicular C-cells in the thyroid gland.
Pentagastrin, a synthetic analog of gastrin, stimulates the C-cells to release calcitonin.
A positive result is suggestive of medullary thyroid cancer.
Why we use Insulin stress test?
to assess the integrity of the hypothalamic-pituitary-adrenal axis.
considered the gold standard for diagnosing hypopituitarism.
In this test, insulin-induced hypoglycaemia should stimulate the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce cortisol. If there’s a deficiency in ACTH due to hypopituitarism, cortisol response will be inadequate.
What are the contraindication of insulin stress test?
epilepsy
ischaemic heart disease
adrenal insufficiency
What are the causes of cushing’s disease?
ACTH dependent causes
1. Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
2. ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
ACTH independent causes
1. iatrogenic: steroids
2. adrenal adenoma (5-10%)
3. adrenal carcinoma (rare)
4. Carney complex: syndrome including cardiac myxoma
5. micronodular adrenal dysplasia (very rare)
Pseudo-Cushing’s
1. mimics Cushing’s
2. often due to alcohol excess or severe depression
3. causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
4. insulin stress test may be used to differentiate
How is acromegaly diagnosed?
- measurement of IGF-1 levels in patients with typical clinical manifestations of acromegaly, especially those with acral and facial features.
- Oral glucose tolerance test
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH - MRI pitutary
When to use Radioiodine treatment?
often used in patients who relapse following ATD therapy or are resistant to primary ATD treatment
contraindications include
1. pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years.
2. Thyroid eye disease is a relative contraindication, as it may worsen the condition
3. the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years
What is the management of thyroid strom?
- symptomatic treatment e.g. paracetamol
- treatment of underlying precipitating event
- beta-blockers: typically IV propranolol
- anti-thyroid drugs: e.g. methimazole or propylthiouracil
- Lugol’s iodine
- dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
Why Oxybutynin should not be used in frail older women with urinary incontinence?
associated with reduced function, confusion and acute delirium.
It is thought that oxybutynin has a higher propensity than other bladder stabilisers to increase dopamine concentration within the brain synaptic clefts resulting in these adverse side effects.
What are the phases of Subacute thyroiditis (also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis)?
occur following viral infection and typically presents with hyperthyroidism.
There are typically 4 phases;
1. phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
2. phase 2 (1-3 weeks): euthyroid
3. phase 3 (weeks - months): hypothyroidism
4. phase 4: thyroid structure and function goes back to normal
what causes hypokalemia with acidosis?
- diarrhoea
- renal tubular acidosis
- acetazolamide
- partially treated diabetic ketoacidosis
What is the Diagnostic thresholds for gestational diabetes?
these have recently been updated by NICE, gestational diabetes is diagnosed if either:
A.fasting glucose is >= 5.6 mmol/L
B. 2-hour glucose is >= 7.8 mmol/L
What are the Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)?
- Fasting 5.3 mmol/l
- 1 hour after meals 7.8 mmol/l, or:
- 2 hour after meals 6.4 mmol/l
What is graves disease and what ab are raised in it?
Autoimmune thyroid disease in which the body produces IgG antibodies to the thyroid-stimulating hormone (TSH) receptor
- TSH receptor stimulating Ab (90%)
- anti-thyroid peroxidase Ab (75%)
What is the diagnostic criteria of DM?
What is the management of Graves disease?
- ATD therapy
carbimazole is started at 40mg and reduced gradually to maintain euthyroidism
typically for 12-18 months.
pt on ATD titration have fewer side-effects than block-and-replace regime
A/E agranulocytosis - Block and replace regime — 1st ATD carbimazole (40mg) blocks. FT4 in reference range then levothyroxine (LT4) is added.
treatment typically lasts for 6-9 months - Radioiodine treatment
1st line t/t for graves disease and toxic nodular goiter.
also used when patients relapse/resistant following ATD
contraindications
i. pregnancy (should be avoided for 4-6 months following treatment)
ii. age < 16 years. Thyroid eye
iii. disease is a relative contraindication, as it may worsen the condition
the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years
- thyroid surgery
what is the MOA , A/E and contraindication for Thiazolidinediones ?
agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance
contraindication:
Heat failure
A/E : weight gain
1. liver impairment: monitor LFTs
2. fluid retention
3. recent studies have indicated 4. an increased risk of fractures
bladder cancer: recent studies have shown bladder ca in pt taking pioglitazone (hazard ratio 2.64)
what are the risk factors of cervical cancer?
- Human papillomavirus (HPV), particularly serotypes 16,18 & 33 is by far the most important factor in the development of cervical cancer. Other risk factors include:
- smoking
- HIV virus
- early first intercourse, many 5. 5. sexual partners
- high parity
- lower socioeconomic status
- combined oral contraceptive pill*
What are the side-effects of glucocorticoids?
- endocrine
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia
Cushing’s syndrome
moon face
buffalo hump
striae - musculoskeletal
osteoporosis
proximal myopathy
avascular necrosis of the femoral head - immunosuppression
increased susceptibility to severe infection
reactivation of tuberculosis - psychiatric
insomnia
mania
depression
psychosis - gastrointestinal
peptic ulceration
acute pancreatitis - ophthalmic
glaucoma
cataracts - suppression of growth in children
- ntracranial hypertension
9.** neutrophilia**
which condition is least associated with hypercalcaemia
monoclonal gammopathy of uncertain significance (MGUS)
What food are high in potassium?
- salt substitutes (i.e. Contain potassium rather than sodium)
- bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
How to take iron tablets?
Fe / Ca carbonate tablets can reduce the absorption of levothyroxine - should be given 4 hours apart.
Iron is best absorbed on an empty stomach.
What is the definative t/t of symtopatic bilateral parathyroid adenomas?
total parathyroidectomy
What is the management of gestational diabetes?
- newly diagnosed women should be seen in a joint diabetes and antenatal clinic within a week
- if the fasting plasma glucose level is < 7 mmol/l : trial of diet and exercise should be offered
- if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
1. if glucose targets are still not met insulin should be added to diet/exercise/metformin
2. gestational diabetes is treated with short-acting, not long-acting, insulin - if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
- if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered.
- glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment
What are the symptoms caused by Pituitary adenomas ?
- excess of a hormone (e.g. Cushing’s disease due to excess ACTH, acromegaly due to excess GH or amenorrhea and galactorrhea due to excess prolactin)
-
depletion of a hormone(s) (due to compression of the normal functioning pituitary gland)
15% non-functioning tumours, therefore, present with generalised hypopituitarism - stretching of the dura within/around the pituitary fossa (causing headaches)
- compression of the optic chiasm (causing a bitemporal hemianopia due to crossing nasal fibers)
What is kallman syndrome?
- cause of delayed puberty secondary to hypogonadotropic hypogonadism.
- inherited as an X-linked recessive trait.
What are the features of kallman syndrome?
- delayed puberty
- hypogonadism, cryptorchidism
- anosmia
- sex hormone levels are low
- LH, FSH levels are inappropriately low/normal
- patients are typically of normal or above-average height
- Cleft lip/palate and visual/hearing defects are also seen in some patients
whta is the interpretation of water deprivation test?
What are the causes of pseudohyponatraemia?
- hyperlipidaemia (increase in serum volume): these substances displace water and hence sodium in the plasma, leading to a falsely low sodium reading.
- *a taking blood from a drip arm.
When parathyroidectomy should be considered in primary hyperparathyroidism?
- Age under 50 years.
- Adjusted serum calcium concentration that is 0.25 mmol/L or more above the upper end of the reference range.
- eGFR < 60 mL/min/1.73 m2 although this threshold depends on other factors, such as age.
- Renal stones on USG or CT.
- Presence of osteoporosis or osteoporotic fracture.
- Symptomatic disease
which drugs cause gynecomastia?
- spironolactone (most common)
- cimetidine
- digoxin
- cannabis
- finasteride
- GnRH agonists e.g. goserelin, buserelin
- oestrogens, anabolic steroids
very rare drug causes of gynaecomastia
* tricyclics
* isoniazid
* calcium channel blockers
* heroin
* busulfan
* methyldopa
What are the changes in thyroid test in preganancy?
↑total T3 and T4 but Nornaml fT3 and fT4 suggest high concentrations of thyroid binding globulin, which can be seen during pregnancy
Which is the prefered ATD in thyroid strom?
propylthiouracil
How is diabetic pt should be screened for diabetic foot disease?
- screening for ischaemia: done by palpating for both the dorsalis pedis pulse and posterial tibial artery pulse
- screening for neuropathy: a 10 g monofilament is used on various parts of the sole of the foot
What is C/F Pseudohypoparathyroidism?
- short fourth and fifth metacarpals
- short stature
- learning difficulties
- obesity
- round face
Bloods
↑ PTH
↓ calcium
↑ phosphate
What is Pseudohypoparathyroidism?
- caused by target cell insensitivity to parathyroid hormone (PTH) due to a mutation in a G-protein.
- type I pseudohypoparathyroidism there is a complete receptor defect
- type II the cell receptor is intact. Pseudohypoparathyroidism is typically inherited in an autosomal dominant fashion.
How to follow up with pt on primary preventive statins?
NICE recommend we follow up patients at 3 months
* repeat a full lipid profile
* if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient
* NICE recommend we consider increasing the dose of atorvastatin up to 80mg
What is t/t of choice for toxic nodular goiter?
Radioiodine therapy
HGV license for DM pt on insulin?
- insulin-treated diabetes can apply for a group 2 (lorry or bus) driving licence if they have no episodes of severe hypoglycaemia within the last 12 months,
- have full awareness of hypoglycaemia
- adequate blood glucose monitoring.
- The patient would need to demonstrate good control of their diabetes and meet these requirements in order to be eligible.
What is feature of insulinoma and how its is diagnosed?
- hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc. Not related to meals.
- rapid weight gain may be seen
- high insulin, raised proinsulin:insulin ratio
- high C-peptide
Diagnosis:
supervised, prolonged fasting (up to 72 hours)
CT pancreas
What advise should be given to pt with hypercalcaemia secondary to malignancy
- Advice about maintaining good hydration (drinking 3-4 L of fluid per day), provided there are no contraindications (such as severe renal impairment or heart failure).
- Reassure that a low calcium diet is not necessary, as intestinal absorption of calcium is usually reduced.
- Advise the person to avoid any drugs or vitamin supplements
- Encourage mobilization
- Advise the person to report any symptoms of hypercalcaemia.
What are Skin disorder for Hypothyroidism and hyperthyroidism?
** hypothyroidism**
* dry (anhydrosis), cold, yellowish skin
* non-pitting oedema (e.g. hands, face)
* dry, coarse scalp hair, loss of lateral aspect of eyebrows
* eczema
* xanthomata
hyperthyroidism
* pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
* thyroid acropachy: clubbing
* scalp hair thinning
* increased sweating
Pruritus can occur in both hyper- and hypothyroidism
What are the causes of addison’s disease?
- Autoimune 80%
- Tuberculosis (<10% in UK)
- metastases (e.g. bronchial carcinoma)
- meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- HIV
- antiphospholipid syndrome
Secondary causes
* pituitary disorders (e.g. tumours, irradiation, infiltration)
C/F of addison’s disease?
- lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
- hyperpigmentation (especially palmar creases)
- ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is cleaved to produce ACTH, other melanocyte-stimulating hormones (MSH) are also produced. This is responsible for skin colour
- primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
- vitiligo
- loss of pubic hair in women
- hypotension
- hypoglycaemia
- hyponatraemia and hyperkalaemia may be seen
- crisis: collapse, shock, pyrexia
What is bartter’s syndrome?
inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle.
C/F of bartters syndrome?
- usually presents in childhood, e.g. Failure to thrive
- polyuria, polydipsia
- hypokalaemia
- normotension
- weakness
When should statins be given in pt with type1 DM?
NICE recommend that we ‘consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes’
atorvastatin 20 mg should be offered if type 1 diabetics who are:
* older than 40 years
* have had diabetes for more than 10 years
* have established nephropathy
* have other CVD risk factors
When we should statins in pt with CKD?
- atorvastatin 20mg should be offered to patients with CKD
- increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and the eGFR > 30 ml/min. If the eGFR is < 30 ml/min a renal specialist should be consulted before increasing the dose
What is the criteria for diagnosis of Metabolic Syndrome?
at least 3 of the following should be identified:
* elevated waist circumference men > 102 cm, women > 88 cm.
* elevated triglycerides: > 1.7 mmol/L
* reduced HDL: < 1.03 mmol/L in males and < 1.29 mmol/L in females
* raised BP: > 130/85 mmHg, or active treatment of hypertension
* raised fasting plasma glucose > 5.6 mmol/L, or previously diagnosed type 2 diabetes
What is the clinical feature of congenital adreal hyperplasia?
Idepending on the specific enzyme deficiency and the severity of the disorder.
Common clinical presentations include:
* virilization
1. female infants may present with ambiguous genitalia due to excessive androgen exposure in utero.
2. male infants appear normal at birth, which can delay diagnosis.
-
salt-wasting crisis
this severe form occurs in about 75% of cases with 21-hydroxylase deficiency
it is characterized by dehydration, hypotension, and electrolyte imbalances, and can be life-threatening if not treated promptly. -
precocious puberty
Excess androgens can lead to early development of secondary sexual characteristics in both males and females. -
infertility
Adults with untreated CAH may experience fertility issues due to hormonal imbalances. - height and growth abnormalities: Children with CAH often experience accelerated growth rates initially but may have a shorter adult stature due to early epiphyseal closure.
What is sick euthyroid syndrome?
In sick euthyroid syndrome (now referred to as non-thyroidal illness) in critically ill pt.
adaptive response to severe illness.
* TSH, thyroxine and T3 is ↓.
* In the majority of cases however the TSH level is within the >normal range
*
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
How to differentiate type 1 DM, type 2 DM and MODY?
Unlike Type 1 diabetes, patients with MODY usually do not present with diabetic ketoacidosis except under severe stress conditions,
MODY : insidious onset with for instance with recurrent balanitis is usual.
unlike Type 2 diabetes, they are often of normal weight and do not exhibit signs of insulin resistance.
How is cortisol test useful in addison’s diseases?
ending a 9 am serum cortisol can be useful:
* > 500 nmol/l makes Addison’s very unlikely
* < 100 nmol/l is definitely abnormal
* 100-500 nmol/l should prompt a ACTH stimulation test to be performed
Which ca are pt with acromegaly are at risk?
colorectal carcinoma
What are the secondary causes of hypercholesterolaemia?
- nephrotic syndrome
- cholestasis
- hypothyroidism
What are the secondary causes of hypertriglyceridaemia?
- diabetes mellitus (types 1 and 2)
- obesity
- alcohol
- chronic renal failure
- drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
- liver disease
Cauaes of nephrogenic DI?
- Familial
- idiopathic
- ↑Ca
- ↓K
- drugs: lithium, demeclocyclin, glibenclamide.
- Sickle cell Anamia
what should be given when a pt have isolated hypertriglyceridaemia and significant cardiac risk factors?
Atorvastatin: fibrates have not been shown to reduce cardiovascular events in the presence of diabetes, while statins have.
What is gitelman’s syndrome?
defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
Features
* normotension
* hypokalaemia
* hypocalciuria
* hypomagnesaemia
* metabolic alkalosis
What is Liddle syndrome?
- rare autosomal dominant condition.
- caused by gain-of-function mutations in the epithelial sodium channel (ENaC) genes, specifically SCNN1B and SCNN1G, which encode the β and γ subunits of the channel.
- hypertension
- hypokalaemic alkalosis.
Causes of hypoglycemia?
- insulinoma - increased ratio of proinsulin to insulin
- self-administration of insulin/sulphonylureas
- liver failure
- Addison’s disease
- alcohol
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion - nesidioblastosis - beta cell hyperplasia
What is Klinefelter’s syndrome?
is associated with karyotype 47, XXY.
Features
* often taller than average
* lack of secondary sexual characteristics
* small, firm testes
* infertile
* gynaecomastia - increased incidence of breast cancer
* elevated gonadotrophin levels but low testosterone
Diagnosis is by karyotype (chromosomal analysis).
Pt with pitutary macroadenoma which is used as an adjunct of transsphenoidal surgery?
octreotide, a somatostatin analogue which is often used as an adjunct to surgery resulting in reduced growth hormone levels and reduction in tumour size.
MOA of Carbimazole
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
C/F of insulinoma
-
hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc
rapid weight gain may be seen
high insulin, raised proinsulin:insulin ratio
high C-peptide
MOA of Meglitinides (e.g. repaglinide, nateglinide)
- increase pancreatic insulin secretion
like sulfonylureas they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells - often used for patients with an erratic lifestyle
- adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas)
electrolyte abnormalities of addison’s disease?
- hyperkalaemia
- hyponatraemia
- hypoglycaemia
- metabolic acidosis
t/t of Type 1DM
Type of insulin
* offer multiple daily injection basal-bolus insulin regimens, rather than twice-daily mixed insulin regimens, as the insulin injection regimen of choice for all adults
* twice-daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin detemir is an alternative.
* offer rapid-acting insulin analogues injected before meals, rather than rapid-acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes
Metformin
NICE recommend considering adding metformin if the BMI >= 25 kg/m²
Feature of Hyperosmolar hyperglycaemic state (HHS).
- hypovolaemia
- marked hyperglycaemia (>30 mmol/L)
- significantly raised serum osmolarity (> 320 mosmol/kg)
can be calculated by: 2 * Na+ + glucose + urea - no significant hyperketonaemia (<3 mmol/L)
- no significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3 - acidosis can occur due to lactic acidosis or renal impairment)
*
What is Riedel’s thyroiditis
- a rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma.
- On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women.
- It is associated with retroperitoneal fibrosis.
Targetes for Type 1 DM
- adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower. NICE do however recommend taking into account factors such as the person’s daily activities, aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia.
-
Blood glucose targets
a. 5-7 mmol/l on waking and
b. 4-7 mmol/l before meals at other times of the day
What is the 1st hormaone to be released in hypogycemia?
Glucagon
What are the features of Hashimoto’s thyroiditis (chronic autoimmune thyroiditis)?
- goitre: firm, non-tender
- anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
associated with
* other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
* Hashimoto’s thyroiditis is associated with the development of MALT lymphoma
What is the t/t of subacute throiditis?
- usually self-limiting - most patients do not require treatment
- thyroid pain may respond to aspirin or other NSAIDs
- in more severe cases steroids are used, particularly if hypothyroidism develops.
C/F of Graves’ disease
Features seen in Graves’ but not in other causes of thyrotoxicosis
* eye signs (30% of patients)
1. exophthalmos
2. ophthalmoplegia
* pretibial myxoedema
* thyroid acropachy, a triad of:
1. digital clubbing
2. soft tissue swelling of the hands and feet
3. periosteal new bone formation
What are the A/E of SGLT-2 inhibitors?
- urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
- normoglycaemic ketoacidosis
- increased risk of lower-limb amputation: feet should be closely monitored
How does SGLT-2 inhibitors cause ketosis?
Hyperureciamia can be associated with ?
hyperlipidaemia, hypertension and Metabolic syndrome
Management of hypothyroidism in pregnanacy
- thyroxine is safe during pregnancy and breastfeeding
- serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
- women require an increased dose of thyroxine during pregnancy
- by up to 50% as early as 4-6 weeks of pregnancy
What is Androgen insensitivity syndrome?
- X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype.
- Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome
What is the C/F of Androgen insensitivity syndrome?
- ‘primary amenorrhoea’
- little or no axillary and pubic hair
- undescended testes causing groin swellings
- breast development may occur as a result of the conversion of testosterone to oestradiol
What is the t/t of prediabetics?
- lifestyle modification: weight loss, increased exercise, change in diet
- at least yearly follow-up with blood tests is recommended
- NICE recommend metformin for adults at high risk ‘whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme’
What is impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)?
- a fasting glucose >= 6.1 but < 7.0 mmol/l implies IFG (due to hepatic insulin resistance).
- IGT (due to muscle insulin resistance) is defined as fasting plasma glucose < 7.0 mmol/l and OGTT 2-hour value >= 7.8 mmol/l but < 11.1 mmol/l
- people with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT.
- patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG.
when does Pt with thyroid eye disease need urgent opltlamology care?
- unexplained deterioration in vision
- awareness of change in intensity or quality of colour vision in one or both eyes
- history of eye suddenly ‘popping out’ (globe subluxation)
- obvious corneal opacity
- cornea still visible when the eyelids are closed
- disc swelling
What is the 1st line t/t of myxoedemic coma?
hydrocortisone and levothyroxine.
What are the MOA of fibrates and A/E?
- through activating PPAR alpha receptors resulting in an increase in LPL activity reducing triglyceride levels.
A/E:
* gastrointestinal side-effects are common
* increased risk of thromboembolism
what is the Management of Hypocalcemia?
- Contamination of blood samples with EDTA may also give falsely low calcium levels.
Management
* severe hypocalcaemia (e.g. carpopedal spasm, tetany, seizures or prolonged QT interval) requires IV calcium replacement
* the preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
* intravenous calcium chloride is more likely to cause local irritation
* ECG monitoring is recommended
* further management depends on the underlying cause
Whta is dynamic pituitary function test?
- To assess patients with suspected primary pituitary dysfunction.
- Insulin, TRH and LHRH are given to the patient following which the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals. Prolactin levels are also sometimes measured*
- A normal dynamic pituitary function test has the following characteristics:
- GH level rises > 20mu/l
- cortisol level rises > 550 mmol/l
- TSH level rises by > 2 mu/l from baseline level
- LH and FSH should double
When is Linagliptins give to T2DM pts?
When it full fills NICE criteria and
Benefits of Linagliptins
* the dose does not need to be adjusted in chronic renal impairment,
* not associated with hypoglycaemia
* can be given alongside low carbohydrate diets.
What are the causes of raided ALP?
Causes of raised alkaline phosphatase (ALP)
* liver: cholestasis, hepatitis, fatty liver, neoplasia
* Paget’s
* osteomalacia
* bone metastases
* hyperparathyroidism
* renal failure
* physiological: pregnancy, growing children, healing fractures
causes of Primary amenorrhoea
- gonadal dysgenesis (e.g. Turner’s syndrome) - the most common causes
- testicular feminisation
- congenital malformations of the genital tract
- functional hypothalamic amenorrhoea (e.g. secondary to anorexia)
- congenital adrenal hyperplasia
- imperforate hymen
What are the causes of Secondary amenorrhoea (after excluding pregnancy)?
- hypothalamic amenorrhoea (e.g. secondary stress, excessive exercise)
- polycystic ovarian syndrome (PCOS)
- hyperprolactinaemia
- premature ovarian failure
- thyrotoxicosis
- Sheehan’s syndrome
- Asherman’s syndrome (intrauterine adhesions)
What is Pendred syndrome?
- autosomal recessive genetic disorder that is characterised by bilateral sensorineural deafness, with mild hypothyroidism (due to defect in the organification of iodine) and a goitre.
- T/t is with thyroid hormone replacement and cochlear implants.
A/E of Exenatide
Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has issued a warning regarding the use of Exenatide, (GLP-1) agonist, due to an increased risk of
* severe pancreatitis
* renal impairment.
what are the A/E of Fibrates ?
- gastrointestinal side-effects are common
- increased risk of thromboembolism
What are the causes of normal Anion gap metabolic acidosis?
- Addison’s
- Bicarbonate loss: GI (e.g. diarrhoea) or renal (e.g. renal tubular acidosis)
- Chloride excess
- Diuretics (e.g. acetazolamide)
Whta should be the tropical t/t of hirsutism in PCOD pt
Eflornithine is a topical cream that works by inhibiting ornithine decarboxylase, an enzyme required for hair growth.
It has been shown to be effective in reducing the growth of unwanted facial hair in women, particularly when other treatments such as combined oral contraceptive pills have failed.
What is the potential effect of subclinical hyperthyroidism?
cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis).
It may also impact on quality of life and increase the likelihood of dementia
Causes of galactorrhoea
pregnancy
prolactinoma
physiological
polycystic ovarian syndrome
primary hypothyroidism
drugs:
phenothiazines, metoclopramide, domperidone,
haloperido
very rare: SSRIs, opioids
Causes of Hyponatraemia with urinary Na >20 mmol/l
Sodium depletion, renal loss (patient often hypovolaemic)
diuretics: thiazides, loop diuretics
Addison’s disease
diuretic stage of renal failure
Patient often euvolaemic
SIADH (urine osmolality > 500 mmol/kg)
hypothyroidism
Causes of Hyponatraemia with urinary Na < 20 mmol/l
Sodium depletion, extra-renal loss
diarrhoea, vomiting, sweating
burns, adenoma of rectum
Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, liver cirrhosis
nephrotic syndrome
IV dextrose
psychogenic polydipsia
What is autoimmune polyendocrinopathy syndrome (APS) type 1?
- APS type 1 is occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC).
- very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21
** Features of APS type 1 (2 out of 3 needed)**
* chronic mucocutaneous candidiasis (typically first feature as young child)
* Addison’s disease
* primary hypoparathyroidism
What is autoimmune polyendocrinopathy syndrome (APS) type 2?
- polygenic inheritance and is linked to HLA DR3/DR4.
- Patients have Addison’s disease plus either:
type 1 diabetes mellitus
autoimmune thyroid disease
Whta are Carbenoxolone?
a synthetic derivative of glycyrrhizinic acid, which is used for the treatment of peptic ulcer.
It has mineralocorticoid activity and can cause** hypokalaemia** not hyperkalaemia.
