Endocrinology Flashcards
Patients with poor compliance will often take a ‘loading dose’ before attending for blood results resulting in an elevated fT4 and TSH
Euglycaemic ketoacidosis is incorrect as this is a side-effect of SGLT2 inhibitors such as.
dapagliflozin
. Fluid retention is a side-effect of***, which would be unlikely to be recommended in this patient with congestive cardiac failure.
thiazolidinediones such as pioglitazone
Kallman syndrome
Hypogonadotrophic hypogonadism , LOW LH AND TESTOSTERONE, Anosmia
Exenatide generally causes weight loss and is therefore useful in obese diabetics but he does not meet the NICE body mass index criteria of 35 kg/m².
Raised prolactin drugs ?
Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
Causes of raised prolactin
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
statins should be discontinued in women 3 months before conception due to the risk of congenital defects
Familial hypercholestrolemia
Leydig cell tumours are sex-chord tumours of the testes or ovaries that secrete testosterone. Male patients commonly present with testicular swelling
. Patients with this condition are genetically male (46XY), yet are phenotypically female with female external genitalia due to a defect in the androgen receptor.
Congenital androgen insensitivity syndrome
NAGMA causes
Causes of NAGMA include (‘ABCD’):
Addison’s
Bicarbonate loss: GI (e.g. diarrhoea) or renal (e.g. renal tubular acidosis)
Chloride excess
Diuretics (e.g. acetazolamide)
Hyperkalemia
Causes of hyperkalaemia:
acute kidney injury
drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin**
metabolic acidosis
Addison’s disease
rhabdomyolysis
massive blood transfusion
Foods that are high in potassium:
salt substitutes (i.e. Contain potassium rather than sodium)
bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
negative acute phase proteins). Examples include:
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
Type 2 DM diagnosis if symptomatic
If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
Impaired glucose tolerance (IGT) is defined
as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
The use of *** in pregnancy should generally be avoided because of the risk of neonatal hypoglycaemia.
sulfonylureas
Diagnostic thresholds for gestational diabetes
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
Hypercalcaemia with suppressed PTH is highly suspicious for*** (e.g. solid organ, or myeloma). Alternative diagnoses which can cause this pattern include thyrotoxicosis.
malignancy( parathyroid-hormone-related peptide release)
Women who smoke are at a two-fold increased risk of developing**** than women who do not
cervical cancer
subacute (De Quervain’s) thyroiditis, given the history of following a viral illness, raised ESR, tender goitre and initial hyperthyroid phase. Ultimately, this condition is usually self-limiting, and simple analgesia is all that is required.
Naproxen
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
***** can also cause diabetes mellitus (along with diabetes insipidus, optic atrophy and deafness)
Wolfram syndrome (DIDMOAD)
/signs should indicate the need for urgent review by an ophthalmologist (see EUGOGO guidelines): in Graves’ disease
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
*** is a rare genetic disorder that affects both males and females. Aromatase deficiency leads to impaired conversion of testosterone to oestradiol and increased circulating levels of testosterone. In females, this can result in ambiguous genitalia, lack of secondary sexual characteristics, and primary amenorrhea
aromatase enzyme deficiency
In diabetes insipidus, the serum is very concentrated (high osmolality) and the urine is very dilute (low osmolality). If the source is central/cranial (lack of ADH production), this can be corrected with desmopressin which will cause the urine to concentrate (higher urine osmolality). If the source is nephrogenic (the kidneys do not respond to ADH), the urine remains dilute (low osmolality) even after desmopressin.
Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
Rx?
The treatment of choice is radioiodine therapy.
*** is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.
Liddle’s syndrome
Treatment is with either amiloride or triamterene
A mutated NCl symporter occurs in the closely associated condition,
Gitelman syndrome.
Barter syndrome is a autosomal recessive condition affecting
Bartter’s syndrome is an 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. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn’s, Cushing’s and Liddle’s syndrome which are associated with hypertension).
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
NICE guidelines clearly stipulate the circumstances under which parathyroidectomy should be considered in primary hyperparathyroidism. These are listed below:
Age under 50 years.
Adjusted serum calcium concentration that is 0.25 mmol/L or more above the upper end of the reference range.
Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 although this threshold depends on other factors, such as age.
Renal stones or presence of nephrocalcinosis on ultrasound or CT.
Presence of osteoporosis or osteoporotic fracture.
Symptomatic disease
Immediate release oxybutynin should, however, be avoided in ‘frail older women’
Use mirabegron , beta 3 agonist
One of the key differentiating features between monoclonal gammopathy of uncertain significance (MGUS) and myeloma is the absence of complications such as immune paresis, hypercalcaemia and bone pain
MGUS stands for monoclonal gammopathy of unknown significance. It is a non-cancerous condition where the body makes an abnormal protein, called a paraprotein.
Although MGUS is not a cancer, people with it have a slightly higher risk of developing:
myeloma (a cancer of blood cells called plasma cells)
lymphoma (a cancer of blood cells called lymphocytes).
MGUS affects plasma cells. These are a type of white blood cell made in the bone marrow. Normal plasma cells make proteins called antibodies to help fight infections. With MGUS, some plasma cells make an abnormal type of antibody called a paraprotein (or M protein). For most people, this does not cause any problems.
Women with hypothyroidism may need to increase their thyroid hormone replacement dose by up to ****as early as 4-6 weeks of pregnancy
50%
pregnancy, there is an increase in the levels of thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.
Therefore need 50 percent increased dose
Primary HPT - PTH ?
Raised/imappropriately normal
A hard and fixed, non-tender thyroid goitre is suggestive of****. This is a rare condition characterised by a fibrotic process associated with mononuclear cell inflammation. It is associated with fibrosing conditions affecting other areas, including retroperitoneal fibrosis and fibrosing mediastinitis. Retroperitoneal fibrosis may not cause symptoms initially and often presents non-specifically with symptoms such as back pain and malaise. A decreased estimated glomerular filtration rate is often present.
Reidel’s thyroiditis, also known as invasive fibrous thyroiditis
AMP-activated protein kinase is a protein that is activated by****, which boosts cellular insulin sensitivity and reduces hepatic glucose production
metformin
The GLP-1 receptor is a protein targeted by GLP-1 receptor agonists such as***. This mimics the incretin effect by increasing the amount of insulin released for a given plasma glucose concentration.
liraglutide
DPP-4 is an enzyme that breaks down incretins such as GLP-1.*** are a class of medications that inhibit DPP-4, thereby prolonging the action of incretin hormones.
Gliptins (e.g. linagliptin)
PPAR gamma receptors are targeted by*** .This increases the sensitivity of peripheral tissues to insulin.
thiazolidinediones (e.g. pioglitazone)
is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
Features
normotension
hypokalaemia
hypocalciuria
hypomagnesaemia
metabolic alkalosis
Gitelman’s syndrome
Carney complex: syndrome including cardiac myxoma
ACTH independent Cushing
MEN-2
Pheochromocytoma
MEN-1
Insuilinoma +
Multiple Endocrine Neoplasia type I (MEN1) is a syndrome characterised by tumours of the parathyroid glands, anterior pituitary, and pancreatic islet cells
HPV risk factors
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****
human immunodeficiency virus
early first intercourse, many sexual partners
high parity
lower socioeconomic status
combined oral contraceptive pill*
MODY
HNF - alpha - T2DM
IPF-1 mutations result in MODY4
Glucokinase mutations can cause MODY2), but this form usually presents with mild hyperglycaemia and is often asymptomatic or mildly symptomatic
HNF-4 alpha mutations result in MODY1, which is a rare cause of monogenic diabetes. Similar to HNF-1 alpha mutations, they lead to early onset type 2 diabetes but are much less common than HNF-1 alpha mutations.
HNF-1 beta, when mutated, leads to MODY5. However, patients with this mutation often present with renal cysts and abnormalities in uterine and genital development along with diabetes
T1DM
Type 1 diabetes mellitus is caused by autoimmune destruction of the Beta-cells of the pancreas. Identical twins show a genetic concordance of 40%. It is associated with HLA-DR3 and DR4. It is inherited in a polygenic fashion
A 35-year-old man presents to his GP with a six-week history of weight gain, cold intolerance, low mood, and headaches. He has a past medical history of primary hyperparathyroidism and underwent parathyroidectomy one year ago.
The following blood tests have been arranged:
Thyroid-stimulating hormone (TSH) 2.3 mU/L(0.5-5.5)
Free thyroxine (T4) 5.6 pmol/L (9.0 - 18)
Prolactin 34 ng/mL (< 20)
The presence of an elevated prolactin level along with secondary hypothyroidism and hypogonadism is indicative of stalk compression is consistent with a non-functioning pituitary adenoma
Microprolactinoma >100 prolactin levels
Pregnant women with GDM targets
Pregnant women with GDM should be advised to maintain their CBGs below the following target levels:
fasting: 5.3mmol/L
AND
1 hour postprandial: 7.8 mmol/L or
2 hours postprandial: 6.4 mmol/L
*** 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, thus preventing PCSK9-mediated LDLR degradation.
Evolocumab
Use of evolocumab is endorsed by NICE under certain conditions only, namely that the dosage is 140mg every 2 weeks and LDL cholesterol is persistently above 3.5 mmol/l.
Hyper parathyroidism surgery referral indication
The NICE guidelines (NG 132) state that all patients with symptomatic hyperparathyroidism or with an adjusted calcium level above 2.85 mmol/mL should be referred to a surgeon with expertise in parathyroid surgery in the first instance.
Drug causes of gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
TD2M: if a triple combination of drugs has failed to reduce HbA1c then switching one of the drugs for a GLP-1 mimetic is recommended, particularly if the BMI > 35
GLP 1 mimetic , liraglutides
A 54-year-old woman presents to the Emergency Department with confusion and fever. She has a past history of thyrotoxicosis previously treated with radioiodine therapy. On examination she has a pulse of 120/min regular, blood pressure 150/90 mmHg, temperature of 39.1ºC and a respiratory rate of 18/min. Examination of the cardiorespiratory system is unremarkable and urine dipstick is clear. Blood results showed the following:
Free T4 84 pmol/l (normal range 10-22 pmol/l)
Free T3 29 pmol/l (2.5-5.5 pmol/l)
TSH < 0.01 mU/l (0.5-4.0 mU/l)
Thyroid storm
Bartter syndrome is aw hypokalemia and
Normotension rather than hypertension ( like in Conns , Cushing , Liddles)
Metabolic syndrome , Syndrome X or Insulin Resistance Syndrome
SIGN recommend using criteria similar to those from the American Heart Association. The similarity of the International Diabetes Federation criteria should be noted. For a 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 blood pressure: > 130/85 mmHg, or active treatment of hypertension
raised fasting plasma glucose > 5.6 mmol/L, or previously diagnosed type 2 diabetes
Other associated features include:
raised uric acid levels
non-alcoholic fatty liver disease
polycystic ovarian syndrome
*** blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
Carbimazole
Acetazolamide
. Acetazolamide is a carbonic anhydrase inhibitor that is used to treat conditions such as glaucoma, altitude sickness and certain types of oedema. It works by reducing the reabsorption of bicarbonate in the proximal tubule of the kidney, leading to metabolic acidosis. The body compensates for this acidosis by increasing potassium excretion in an attempt to retain more hydrogen ions, which can result in hypokalaemia
Hypokalemia with acidosis
Hypokalaemia with acidosis
diarrhoea
renal tubular acidosis
acetazolamide
partially treated diabetic ketoacidosis
** is an autosomal recessive genetic disorder that is characterised by bilateral sensorineural deafness, with mild hypothyroidism and a goitre. The patients tend to present with progressive hearing loss and delay in academic progression. Often head trauma tends to make the sensorineural deafness worse, leading to patients having to avoid contact sports.
Pendred
Albright’s hereditary osteodystrophy (pseudohypoparathyroidism)
short 4th and 5th metacarpals. This feature is typically seen in conditions such as**, which presents with a constellation of symptoms including short stature, round face, subcutaneous calcifications, and resistance to parathyroid hormone.
***, an alpha-adrenergic receptor antagonist, is employed preoperatively to manage hypertension associated with pheochromocytomas. While such tumours often cause headaches similar to those reported by our patient, they are typically accompanied by palpitations and sweating
Phenoxybenzamine
SIADH Rx
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
SIADH Rx
patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG
patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG
Screening for gestational diabetes
the oral glucose tolerance test (OGTT) is the test of choice
women who’ve previously had gestational diabetes: OGTT should be performed as soon as possible after booking and at 24-28 weeks if the first test is normal. NICE also recommend that early self-monitoring of blood glucose is an alternative to the OGTTs
women with any of the other risk factors should be offered an OGTT at 24-28 weeks
Anaplastic thyroid cancer
. Anaplastic thyroid cancer is a rare, aggressive type of thyroid cancer that typically presents with rapidly enlarging neck mass, hoarseness, and dyspnoea due to compression of the trachea and laryngeal nerve involvement. The patient’s history of toxic multinodular goitre treated with radioiodine may have increased her risk for developing anaplastic thyroid cancer. Additionally, the presence of vocal cord paralysis and external compression of the trachea on laryngoscopy support this diagnosis.
*** In this state (i.e. during an intercurrent severe illness) we would expect low levels of free T4, free T3 and TSH.
Sick euthyroid .
In pregnancy, there is an increase in the levels of thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.
The presence of tendon xanthomata and cholesterol levels meet the diagnostic criteria for familial hypercholesterolaemia. Homozygous familial hypercholesterolaemia is exceedingly rare - most patients die in their teenage years from a myocardial infarction.
Pregnancy and TBG
Elevated oestrogen levels produced in pregnancy stimulate the expression of thyroid binding globulin (TBG) from the liver. As TBG binds to free thyroxine (fT4) and free triiodothyronine (fT3), an increase in TBG results in an initial lowering of fT4 and fT3. This in turn causes a secondary increase in thyroid-stimulating hormone (TSH). The net result is a new equilibrium between free and bound thyroid hormones with an increase in bound-T3 and T4 but an overall unaffected fT3 and fT4 level. As it’s the fT4 and fT3 that are responsible for clinic features of thyrotoxicosis these cases rarely produce clinical signs or symptoms, nor do they require treatment.
Alcohol and hypoglycaemia
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
impairs the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, leading to cortisol deficiency and excess androgen production
21-hydroxylase deficiency (90%). CAH
11-beta hydroxylase deficiency
results in hypertension due to excess deoxycorticosterone
leads to mineralocorticoid excess with low androgen and estrogen levels
17-hydroxylase deficiency (very rare)
Pioglitazone , thiazolidinediones inthibitor
Adverse effects
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype.
Androgen insensitivity syndrome
is the set of symptoms that result from two or more X chromosomes in males. The primary features are infertility and small poorly functioning testicles. It is characterised by low testosterone levels with increased levels of FSH and LH.
Klinefelter syndrome (47,XXY)
T1DM and statins
NICE specifically state that we should not use QRISK2 for type 1 diabetics. Instead, the following criteria are used:
older than 40 years, or
have had diabetes for more than 10 years or
have established nephropathy or
have other CVD risk factors
Thyroid malignancy
May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
Vascular invasion predominates
Multifocal disease raree
Follicular carcinoma
bilateral idiopathic adrenal hyperplasia is the most common cause for
Primary hyperaldosteronism
** is a more slow-growing form of thyroid cancer. Although more common than thyroid lymphoma, it is usually seen in a younger demographic and is not associated with Hashimoto’s thyroiditis.
Papillary thyroid cancer
This is characterised by inflammation of the thyroid gland, following which normal thyroid tissue is replaced by fibrous tissue. This leaves a hard, woody goitre on palpation
Riedel’s thyroiditis
