Endocrine passmedicine (2)
Terms in this set (71)
A 85-year-old male presents to clinic for a review of his overactive bladder. Non-pharmacologic treatments have so far failed to improve his symptoms. Which of the following pharmacotherapies represents the most appropriate initial management step?
NICE (Feb 2015) outlines treatment steps for the management of overactive bladder symptoms in men.
If non-pharmacologic measures fail, an anticholinergic agent is first line.
In older men,tolterodine is preferred to oxybutynin as the latter has a greater risk of causing confusion.
If anticholinergics fail or are contraindicated, mirabegron may be trialled. Its mechanism of
action is via beta-adrenoreceptor-mediated relaxation of the bladder wall.
Tamsulosin is an alpha-blocker and indicated if the patient if has obstructive symptoms, rather than symptoms of overactive bladder
Finasteride is a 5-alpha reductase inhibitor and indicated if the patient has obstructive
symptoms and an enlarged prostate with a high risk of progression.
Desmopressin is a synthetic vasopressin analogue that acts in the collecting duct of the
nephron. It is sometimes used off-label for nocturnal urinary incontinence.
TSH 9.2 mu/L
Free thyroxine 14 pmol/L
She is currently well and asymptomatic. What is the most appropriate management?
Repeat TFTs in a few months time
This patient has subclinical hypothyroidism.
TSH raised but T3, T4 normal
no obvious symptoms
risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
risk increased by presence of thyroid autoantibodies
TSH > 10
thyroid autoantibodies positive
other autoimmune disorder
previous treatment of Graves' disease
***Frequency of TFT testing :
if anti-TPO antibodies are negative and asymptomatic Review every 3 years with thyroid function tests
Where antibodies are positive, a 1-year testing interval is recommended for patients without symptoms of hypothyroidism.
A middle-aged man with type 2 diabetes mellitus . Despite weight loss, metformin
and gliclazide his HbA1c is 68 mmol/mol (8.4%). The patient agrees to start insulin therapy.
which type of insulin should be tried initially?
Basal bolus regime
Isophane (NPH insulin)
Neutral Protamine Hagedorn (NPH) insulin [also known as isophane insulin] (injected once or twice daily according to need should be offered.
NPH plus a short-acting insulin should be considered (particularly if the person's HbA1c is
75 mmol/mol [9.0%) or higher). This may be administered either separately or as a pre-
mixed (biphasic) human insulin preparation.
Insulin detemir or insulin glargine should be considered as an alternative to NPH insulin if
→ The person needs assistance from a carer or healthcare professional to inject insulin and
the use of insulin detemir or insulin glargine would reduce the frequency of injections from twice to once daily,
.The person's lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes, or
.The person would otherwise need twice-daily NPH insulin injections in combination with oral antidiabetic drugs.
A 62-male co hypertension and proximal myopathy. On examination he is noted to have abdominal striae. Which one of the following is most associated with ectopic
Small cell lung cancer
Squamous cell lung cancer
Small cell lung cancer accounts 50-75% of case of ectopic ACTH
Adrenal carcinoma and cardiac myxoma are causes of ACTH independent Cushing's syndrome
Uncontrolled Bp despite 3 oral anti-hypertensive medications
BMI 28, k 3.2, KFT normal
CT abdomen: Right adrenal adenoma
Which of the following is the most likely diagnosis?
Renal artery stenosis
The relatively normal weight, coupled with hypertension and hypokalaemic metabolic alkalosis fits well with a diagnosis of Conn's syndrome, (primary hyperaldosteronism).
The right adrenal
adenoma is the likely source of excess aldosterone production.
Cushing's syndrome is unlikely given that the body mass index is only slightly elevated, and the
presence of an adrenal adenoma and biochemical abnormalities effectively rules out essential
Phaeochromocytoma may be associated with hypokalaemia, but is more likely to be associated with episodic hypertension associated with bursts of catecholamine release.
In renal artery stenosis, a significant rise in creatinine would be expected
A 55-year-old woman have osteoporotic hip fracture.
Free T4 29
Which one of the following autoantibodies is most likely to be present?
TSH receptor stimulating autoantibodies
Anti-thyroid peroxidase autoantibodies
TSH receptor stimulating autoantibodies (often referred to as Thyroid Stimulating
Immunoglobulins) are almost diagnostic of Graves' disease, the most common cause of thyrotoxicosis in UK
Recurrent attack of hypoglycaemia
His medication on admission is as follows:
Metformin 1g bd
Gliclazide 160mg od
Pioglitazone 45mg od
Aspirin 75mg od
Simvastatin 40mg on
What is the most appropriate initial action?
Make no changes to the medication
Stop all oral antidiabetic medications
Neither metformin nor pioglitazone cause hypoglycaemia. T
he gliclazide dose is therefore responsible and should be stopped whilst deciding upon longer term changes to his medication.
Acromegaly: increased sweating is caused by?
sweat gland hypertrophy
Caused of ketone production during diabetic ketoacidosis?
The low-insulin conditions seen in diabetic ketoacidosis stimulate the process of lipolysis and the production of the ketone bodies, beta-hydroxybutyrate and acetoacetate, which can be used as metabolic fuel.
Can ferrous sulfate affect Thyroid function tests ?
Iron reduces the absorption of thyroxine
weight gain, impotence and
hypertension. notice purple striae around his abdomen. generalised decreased muscle strength. Given the likely underlying diagnosis, what are the urea and electrolytes most likely to show?
Cushing's syndrome - hypokalaemic metabolic alkalosis
Which one of the following adverse effects is linked to long-term steroid use?
Long-term corticosteroid use is linked to osteopaenia and osteoporosis, rather than osteomalacia.
Avascular necrosis (AVN) is a death of bone tissue secondary to loss of the blood supply. This leads to bone destruction and loss of joint function.
It most commonly affects the epiphysis of long bones such as the femur.
long-term steroid use
pain in the affected joint
plain x-ray findings may be normal initially
MRI is the investigation of choice. It is more sensitive than radionuclide bone scanning
be treated with lifelong warfarin with target INR 2-3
Deafness and hypothyroidism?
The patients tend to present with :
progressive hearing loss
delay in academic progression.
Often head trauma tends to make the sensorineural deafness worse, leading to patients having to avoid contact sports.
euthyroid or mild hypothyroidism
Thyroid function tests are also often normal, requiring the perchlorate discharge test to aid diagnosis.
diagnosed via :
genetic testing (Pendred syndrome (PDS) gene, chromosome 7),
audiometry and MRI imaging to look for characteristic one and a half turns in the cochlea, compared to the normal two and a half turns.
thyroid hormone replacement
Which one of the following is least associated with hypercalcaemia?
Squamous cell lung cancer
Monoclonal gammopathy of uncertain significance
Monoclonal gammopathy of uncertain significance
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
A 16-year-old male co lack of pubertal development his testes are undescended and there is only scanty pubic hair. What is the most likely diagnosis?
Cryptorchidism is more suggestive of Kallman's than Klinefelter's syndrome
Kallman's syndrome is a recognised cause of delayed puberty secondary to hypogonadotrophic hypogonadism.
It is usually inherited as an X-linked recessive trait.
***cryptorchidism (Cryptorchidism is more suggestive of Kallman's than Klinefelter's syndrome)
Cryptorchidism is the absence of one or both testes from the scrotum (undescended testis).
anosmia (*Lack sense of smell) present in 75%
Cleft lip/palate and visual/hearing maybe seen
sex hormone levels are low
patients are typically of normal or above average height
LH, FSH levels are inappropriately low/normal
Lack of development of secondary sexual characteristics
*no mental retardation
Fluorescent in situ hybridisation (FISH) is currently the best means of a genetic diagnosis
Absent olfactory bulbs are present on 75% of MRI scans in these patients.
For a male who begin a relationship with a woman
Pulsed (NOT Continuous) GnRH treatment is needed to restore LH and FSH release.
Once his family is complete, switching to testosterone therapy may be more convenient for him.
Although Testosterone supplementation will restores secondary sexual characteristics, it doesn't restore fertility and is therefore not appropriate here.
FSH can be used to induce fertility, but it is less effective than pulsed GnRH therapy.
LH can be used in conjunction with FSH to induce fertility in women with Kallmann syndrome.
goitre containing multiple irregular nodules. Nuclear scintigraphy with technetium 99m reveals patchy uptake. What is the treatment of choice?
Toxic multinodular goitre (TNG) (Plummer's disease)
Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules that secrete excess thyroid hormones.
TNG is the second most common cause of hyperthyroidism in the Western world, after Graves disease. In elderly individuals and in areas of endemic iodine deficiency, TNG is the most common cause of hyperthyroidism.
usually occurs in women aged over 55 years
Evidence of hyperthyroidism (↓TSH + or normal free T4)
Nuclear scintigraphy reveals ***patchy uptake
---------------------------- Toxic nodular goiter (TNG) ➡️patchy uptake
Graves disease ➡️ homogeneous diffuse uptake.
Thyroiditis ➡️ low uptake.
CT of the chest is the investigation of choice to determine the degree of retrosternal involvement Ultrasonography is a highly sensitive to detect nodules that are not palpable during thyroid examination.
The treatment of choice is ***radioiodine therapy
Patients should not have close contact with children under the age of 11 years for about 2 weeks after treatment
A 45-year-old man presents with bitemporal hemianopia and spade-like hands. What is the definite test to confirm the diagnosis?
Early morning growth hormone
Insulin tolerance test
Oral glucose tolerance test with growth hormone measurements
Random insulin-like growth factor 1 (IGF-1)
Short ACTH test
The diagnostic test for acromegaly is an oral glucose tolerance with growth hormone measurements
Acromegaly (excess growth hormone ''GH'')
Approximately 30% of growth hormone (GH) secreting pituitary tumours is associated with mutation of the *Gs protein alpha subunit
Pituitary adenoma (95%)
ectopic GHRH or GH production by tumours e.g. pancreatic
GH secreting tumours ➡️ mutation in the alpha sub-unit of the stimulatory guanosine triphosphate (GTP) binding protein➡️persistent elevation of cyclic adenosine monophosphate (cAMP) ➡️production of excess growth hormone.
coarse facial appearance, spade-like hands, increase in shoe size
large tongue, prognathism, interdental spaces
excessive sweating and oily skin
**Pseudogout is a recognised association of acromegaly; gout is not.
Hypertension, heart failure and *cardiomyopathy may occur.
Goitre is seen in 20%, along with other soft tissue swelling.
*Phosphate levels are elevated but calcium levels are not significantly increased.
features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases galactorrhoea
6% of patients have MEN-1
***risk for colon cancer ( regular colonoscopy screening, starting at the age of 40 years)
Trans-sphenoidal surgery is first-line treatment for acromegaly in the majority of patients
Somatostatin analogue (eg: octreotide)
first line medical therapy.
Long acting somatostatin analogue, Somatuline LA (Mode of action ↓↓meal-time related superior mesenteric artery blood flow)
Dopamine agonists (eg: bromocriptine)
Pegvisomant the major use of pegvisomant is in patients who have an inadequate response to surgery or radiotherapy (is a third-line treatment when surgery, radiotherapy and somatostatin analogues are not effective.)
most likely cause of death if treatment is unsuccessful?
Left ventricular failure
Which one of the following is the most common non-iatrogenic cause of Cushing's syndrome?
Ectopic ACTH production
Micronodular adrenal dysplasia
Cushing's disease is the most common, non-iatrogenic, cause of Cushing's syndrome
What is the mechanism of action of exenatide?
Glucagon-like peptide-1 (GLP-1) mimetic
A 25-year-old male develops type 2 diabetes mellitus. Which one of the following genes is most likely to be responsible?
Maturity-onset diabetes of the young ( MODY)
***family history of early onset diabetes is often present
autosomal dominant condition.
characterised by the development of type 2 diabetes mellitus in patients < 25 years old.
It is an important diagnosis as the therapy may be different compared with T1DM and T2DM.
MODY3 is particularly important to diagnose as many patients initially treated with insulin can in fact be managed with sulphonylurea.
the commonest form of MODY, 60% of cases
due to a defect in the HNF-1 alpha gene (hepatic nuclear factor-1)
↑ (HDL) cholesterol levels
Preserved insulin sensitivity
Low renal threshold for glucose (glycosuria)
Sulphonylureas is the initial drug of choice
The second commonest MODY variant after MODY3
20% of cases
due to a defect in the glucokinase gene (GCK gene)
Defect in HNF-1 beta gene.
associated with renal cysts, uterine abnormalities and gout as well as diabetes.
(Often the renal cysts can be detected in the womb before a baby is born.
**bilateral renal cysts + glucose = MODY related cyst formation)
insulin treatment is usually necessary
What is the mechanism of action of thiazolidinediones?
PPAR-gamma receptor agonist
Glitazones are agonists of PPAR-gamma receptors, reducing peripheral insulin resistance
Women with thyrotoxicosis. Recent blood
T4 25 pmol/l
Anti-thyroid peroxidase antibodies 115 (< 35)
A smooth, non-tender goitre is noted . The patient also has
exophthalmos although there is no ophthalmoplegia, no reduction in visual acuity and no eye symptoms present.
What is the most appropriate management?
This patient has Graves' disease as evidenced by the thyrotoxicosis, goitre, thyroid eye disease
and anti-thyroid peroxidase antibodies.
Radioiodine treatment should be avoided given the presence of thyroid eye disease so
carbimazole is a better treatment option.
If her eye disease was severe then an ophthalmologist should be consulted.
Options for severe thyroid eye disease include systemic steroids and radiotherapy.
A 87-year-old woman who has a BMI of 44 kg/m"2 undergoes a Roux-en-Y gastric bypass. Of which vitamin/mineral is she most likely to require supplementation?
The duodenum is the primary site of absorption for both iron and calcium. All gastric bypass operations bypass the duodenum. Nearly all menstruating women will therefore require iron supplementation.
suspected insulinoma, which one of the following is considered the best
Oral glucose tolerance test
Insulin tolerance test
Early morning C-peptide levels
Glucagon stimulation test
Insulinoma is diagnosed with supervised prolonged fasting
CT of the pancreas is also useful in demonstrating a lesion
(GLP-1) Mimetics (e.g. exenatide)
***hormone released by the small intestine in response to an oral glucose load
(In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be ↓ in T2DM.)
• ↑ insulin secretion and inhibit glucagon secretion
• Licensed for use in T2DM
• Must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal
• May be combined with metformin, a sulfonylurea or a thiazolidinedione
• Typically results in weight loss
• Major adverse effect is nausea and vomiting
• The Medicines and Healthcare products
***increased risk of severe pancreatitis, increased risk of renal impairment
• Should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35
kg/m 2 ) and the need for high dose insulin is likely
• Continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% in 6 months)
Exenatide should only be used in combination with Metformin, a Sulfonylurea or both.
Dipeptidyl Peptidase-4 inhibitors
(DPP-4) Inhibitors (e.g. Vildagliptin, sitagliptin)
• Oral preparation
• Trials show that the drugs are relatively well tolerated with no ↑ incidence of hypoglycemia
• Do not cause weight gain
• Continue DPP-4 inhibitor only if there is ↓ of > 0.5 percentage points in HbA 1 c in 6 months
• 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
Thiazolidinediones are a new class of agents used in the treatment of type 2 diabetes mellitus.
They are agonists to the PPAR-gamma receptor and ↓ peripheral insulin resistance
Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma receptor) is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function
• **Weight gain
• Liver impairment: monitor LFTs
• **Fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is ↑
if the patient also takes insulin
• Recent studies have indicated an ↑ risk of fractures
• *Rosiglitazone is not recommended for use in patients with ischemic heart disease or peripheral arterial disease. The risk of complications may be ↑ if rosiglitazone is combined with insulin
• Only continue if there is a reduction of > 0.5 percentage points in HbA 1 c in 6 months
Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus.
They work by increasing pancreatic insulin secretion and hence are only effective if functional B cells are present.
Common adverse effects
• Hypoglycaemic episodes (more common with long acting preparations such as chlorpropamide)
• ↑ appetite and weight gain
Rarer adverse effects
• Syndrome of inappropriate ADH secretion
• Bone marrow suppression
• Liver damage (cholestatic)
• Peripheral neuropathy
• Sulfonylureas should be avoided in breast feeding and pregnancy
Metformin is a **biguanide used mainly in the treatment of type 2 diabetes mellitus.
Unlike sulphonylureas it does not cause hypoglycemia and weight gain and is therefore first-line if the patient is overweight.
Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease
Mechanism of action
• ↑ Insulin sensitivity
• ↓ hepatic gluconeogenesis
• May also ↓ gastrointestinal absorption of carbohydrates
*Gastrointestinal side-effects are more likely to occur if metformin is not slowly titrated up. The BNF advises leaving at least 1 week before increasing the dose.
• Gastrointestinal upsets are common (nausea, anorexia, diarrhea), intolerable in 20%
• ↓ vitamin B12 absorption - rarely a clinical problem
• Lactic acidosis* with severe liver disease or renal failure
• High dose (>2gm) interferes with enterohepatic circulation of bile salt → diarrhea.
• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 µmol/l and stopping metformin if > 150 µmol/l
• Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis)
• Alcohol abuse is a relative contraindication
• Stop 2 days before general anaesthetic, restart when renal function normal
• Stop prior to IV contrast e.g. Angiography, restart when renal function normal
Fasting glucose 7.7 mmol
HbAlc 5 mmol
Which one of the following would explain the discrepancy between the HbA1c and fasting
Vitamin B12 deficiency
Raised cholesterol level
A history of alcohol excess
Glycosylated haemoglobin (HbA1c)
HbA1c is produced by the glycosylation of haemoglobin at a rate proportional to the glucose concentration.
HbA1c is generally thought to reflect the blood glucose over the previous '2-3 months' although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 weeks
The level of HbA1c therefore is dependant on
red blood cell lifespan
average blood glucose concentration
HbA1c is affected by many factors:
Elevated HbA1c can occur in iron deficiency, vitamin B 12 deficiency, alcohol dependence, chronic renal failure, hyperbilirubinaemia and splenectomy
Reduced HbA1c can occur in chronic liver disease, hypertriglyceridaemia, some haemoglobinopathies, splenomegaly, rheumatoid arthritis and certain medications, including iron or vitamins B 12 , C or E, antiretrovirals and dapsone.
primary mode of action of orilistat?
The primary mode of action of orilistat is to inhibit pancreatic lipases, which in turn will decrease the absorption of lipids from the intestine
Pt manged for DKA and become confused, irritable and was slurring her words., What is the most likely cause of her new neurological symptoms?
Cerebral oedema is an important complication of fluid resuscitation in DKA, especially in
Children/young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual
disturbance, focal neurology etc.
It usually occurs 4-12 hours following commencement of treatment but can be present at any time.
If any suspicion, request a CT head
A 72-year-old woman presents with polyuria and polydipsia. Investigations reveal the following:
Fasting glucose 4.5 m
Parathyroid hormone 6 pmol/L (normal range-0.8-8.5)
What is the most likely underlying diagnosis?
Vitamin D excess
The PTH level in primary hyperparathyroidism may be normal
Despite a raised calcium level the parathyroid hormone level is inappropriately normal. This points towards a diagnosis of primary hyperparathyroidism and the other causes (such as myeloma) would lead to a suppression of parathyroid hormone
Which one of the following regarding the management of thyroid problems during pregnancy is
- Maternal free thyroxine levels should be kept in the upper third of the normal reference
range when treating thyrotoxicosis
- Increased levels of thyroxine-binding globulin are seen in pregnancy
- Block-and-replace is preferable in pregnancy compared to antithyroid drug titration
- Breast feeding is safe whilst on thyroxine
- Untreated thyrotoxicosis increases the risk of premature labour
Propylthiouracil (PTU) has traditionally been the antithyroid drug of choice.
Propythiouracil is more highly protein bound and is ionized at pH 7.4, thus making it less likely to cross the placenta or breast milk. PTU is the most appropriate treatment for pregnant who plan to breast-feed her baby after delivery.
Due to the small risk of fetal abnormalities with carbimazole it is recommended to use PTU in the first trimester during organogenesis and then carbimazole in trimester 2 + 3.
Carbimazole is the recommended option in late pregnancy because of reports of hepatotoxicity associated with Propylthiouracil.
pregnancy ➡️⬆️ thyroxine-binding globulin (TBG)➡️⬆️total thyroxine but does not affect the free thyroxine level
in normal pregnancy (T3 ) and T4 levels show a slight increase with suppressed (TSH) in the first trimester due to the partial thyroid-stimulating action of human chorionic gonadotrophin (beta-HCG).
A pregnant woman with positive thyroid antibodies but who is euthyroid has a higher risk of spontaneous abortion. A meta-analysis confirms the association between anti-TPO antibodies and premature foetal loss.
thyroid eye disease is suspected. What can be said regarding her thyroid status?
Hyper- or euthyroid
Hypo- or euthyroid
Eu-, hypo- or hyperthyroid
Whilst thyroid eye disease is mostly associated with hyperthyroidism secondary to Graves' disease there is not always an association. A minority of patients will either be euthyroid or
It is also known that the severity of thyroid eye disease is not related to the degree of thyrotoxicosis in Graves' disease.
thyroid eye disease and is being considered for radiotherapy. Over the past three days her right eye has become red and painful. On examination there is proptosis and erythema of the right eye. Visual acuity is 6/9 in both eyes. What complication is she most likely to have
Central retinal vein occlusion
likely to be caused by pioglitazone?
What is the most common cause of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia is the most common cause of primary hyperaldosteronism
Which of the following findings is most consistently seen in polycystic ovarian syndrome?
Ovarian cysts on ultrasound
Raised LH:FSH ratio
Polycystic ovarian syndrome - ovarian cysts are the most consistent feature
Whilst all of the features listed above may be seen in polycystic ovarian syndrome, ovarian cysts are the most consistent feature.
23 y woman, She has not a normal period for around 8 months now. A recent pregnancy test was negative.
FSH 2.2 IU/L (0-20 IU/L)
Oestradiol 84 pmol/I (100-500 pmol/l)
TSH 3.1 mIU/L
Prolactin 2 ng/ml (0-10 ng/ml)
Free androgen index 3 ( <7)
What is the most likely cause of her symptoms?
Premature ovarian failure
Polycystic ovarian syndrome
The bloods show a hypothalamic amenorrhoea which may be caused by stress or excessive exercise. The FSH would be raised in premature ovarian failure.
Causes of primary amenorrhoea
congenital adrenal hyperplasia
congenital malformations of the genital tract
Secondary amenorrhoea is defined as when menstruation has previously occurred but has now stopped for at least 6 months.
Causes of secondary amenorrhoea (after excluding pregnancy)
***hypothalamic amenorrhoea (e.g. Stress, excessive exercise)⬆️FSH
polycystic ovarian syndrome (PCOS)
premature ovarian failure⬆️FSH
thyrotoxicosis (hypothyroidism may also cause amenorrhoea)
Asherman's syndrome (intrauterine adhesions)
exclude pregnancy with urinary or serum bHCG
gonadotrophins: low levels indicate a hypothalamic cause where as raised levels suggest an ovarian problem (e.g. Premature ovarian failure)
androgen levels: raised levels may be seen in PCOS
thyroid function tests
Primary ovarian failure means that the patient never has a normal menstrual cycle, and has the triad of
2- hypergonadotropinism, 3- and hypoestrogenism.
A 62-year-old HGV driver is reviewed. He was diagnosed last year with type 2 diabetes mellitus. Following weight loss and metformin his HbA1c has decreased from 74 mmol/mol (8.9%) to 68 mmol/mol (8.4%). What is the most suitable next step in management?
Make no changes to management
Stop metformin for a period to ensure hypoglycaemic awareness is not lost
Pioglitazone is the best option here as it would not put him at risk of hypoglycaemia, which obviously could be dangerous given his job. The NICE guidelines would also support the use of a DPP-4 inhibitor (e.g. sitagliptin or vildagliptin) in this situation.
Dm HBA1C 8.4 DVLA
He may be able to apply for a HGV licence if he meets strict criteria relating to hypoglycaemia
most important modifiable risk factor for the development of thyroid eye disease is
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.
Which one of the following types of bariatric surgery is most likely to cause significant
Laparoscopic-adjustable gastric banding
Roux-en-Y gastric bypass surgery
Biliopancreatic diversion with duodenal switch
Biliopancreatic diversion with duodenal switch is a primarily malabsorptive procedure and reserved for patients who are very obese.
type 2 diabetes mellitus has poor glycaemic control (63 mmol/mol). And stop taking gliclazide due to repeated episodes of hypoglycaemia and is only taking maximum dose metformin. Her BMI is 26 kg/mA2. What is the most appropriate next step in
Add either pioglitazone, a DPP-4 inhibitor or a SGLT-2 inhibitor
Refer her for a laparoscopic gastric band
Refer her for insulin therapy
Add either a thiazolidinedione or exenatide
Add either a DPP-4 inhibitor or exenatide
Add either pioglitazone, a DPP-4 inhibitor or a SGLT-2 inhibitor
Potential complications of Paget's disease include each of the following except:
Pt treated for DKA Which of the following thyroid function tests results would be in keeping with her presentation?
TSH high, T4-Low, T3 high
TSH- high, T4-normal, T3 normal
TSH-low, T4-Low, T3 high
TSH-low, T4-normal, T3 normal
TSH-normal, T4 -Low, T3 low
TSH - normal, T4 - Low, T3 low
Sick euthyroid syndrome is a reversible state of abnormal thyroid function tests due to a non-thyroidal illness, without pre-existing hypothalamic-pituitary or thyroid gland dysfunction.
By definition, after recovery of the non-thyroidal illness, thyroid function tests should revert back to normal
Causes of sick euthyroid include: myocardial infarctions, starvation, burns, trauma, surgery
malignancy, diabetic ketoacidosis, any organ failure and inflammatory conditions.
The pathology postulated is the down regulation of type 1 deiodinase, reducing the peripheral conversion of T4 to T3 and thus reducing the basal metabolic rate during periods of stress.
Upregulation of type 3 deiodinase to inactive (reverse) T3 also aids to reducing basal metabolic
What is the mechanism of action of carbimazole ?
Blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on
Other examples of muscarinic antagonists used in urinary incontinence include oxybutynin and solifenacin. Examples of muscarinic antagonists used in different conditions include ipratropium chronic obstructive pulmonary disease) and procyclidine (Parkinson's disease).
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Dipeptidyl peptidase-4 (DPP-4) inhibitors
induce Glucose dependent glucagon suppression
only recommended as second-line therapy with metformin if patients are at significant risk of hypoglycaemia or its consequences (e.g. older patients, those working at heights or heavy machinery, isolated patients) or if a sulphonylurea is not tolerated or contraindicated.
continue DPP-4 inhibitor only if there is a reduction of > 0.5 percentage points in HBA1c in 6 months
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
well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain
GI disturbance is reported across a range of sitagliptin studies, including nausea, flatulence, diarrhoea and constipation.
A decision is made to start her on degludec liraglutide
Which of the following should you warn her about?
Patients often get skin nodules around the injection site
Pancreatitis is commonly associated with treatment
Risk of hypoglycaemia will increase when she starts treatment
She will lose approximately 5kg in weight when she starts treatment
She will gain approximately 6kg in the first year of treatment
insulin and GLP-1 fixed dose combinations are increasingly attractive as a treatment option for
diabetologists because they combine the potent glucose-lowering effect of GLP-1 agonists and
long-acting insulin analogues in one preparation.
They are however associated with increased
risk of hypoglycaemia
Skin nodules are most often seen around injection sites when modified release systems are used for delivering GLP-1, such as those used in weekly exenatide, (microspheres).
Pancreatitis features in case reports associated with the use of GLP-1 agonists, although no consistent link
has been established.
Modest weight loss is seen when patients start degludec / liraglutide
against a background of oral agents, but this is less than that seen for patients who start
two month history of lethargy. Blood
Na 129 mmol/l
Urea 5.1 mmol/l
K 5.3 mmol/
Creatinine 99 μmol/l
Total T4 66 nmol/I
Which one of the following investigations is most likely to reveal the diagnosis?
Overnight dexamethasone suppression test
Short synacthen test
The short synacthen test is the best test to diagnose Addison's disease
Hyponatraemia and a high potassium in a patient with lethargy is highly suggestive of Addison's disease.
The thyroxine level is slightly low and she may indeed have co-existing hypothyroidism
but this would not explain the high potassium
Many labs have an upper reference range for potassium of 5.5 mmol/l, but in the context of the other results hypoadrenalism should be suspected
diagnosed as having primary atrophic hypothyroidism 12 months ago recent thyroid function tests (TFTs):
TSH 12.5 mU/
Free T4 14 pmol/i
She is currently taking 75mcg of levothyroxine once a day. How should these results be
Poor compliance with medication
Her thyroxine dose needs to be increased
Evidence of recent systemic steroid therapy
She is on the correct dose
T4 to T3 conversion disorder
The TSH level is high. This implies that over recent days/weeks her body is thyroxine deficient. However, her free T4 is within normal range.
The most likely explanation is that she started taking the thyroxine properly just before the blood test. This would correct the thyroxine level but the TSH takes longer to normalise.
A 68-year-old woman is found to have the following blood tests:
Free T4 19 pmol/l (range 12-25)
Free T3 7 pmol/I (range 3-9)
If left untreated, what are the most likely possible consequences?
Supraventricular arrhythmias and osteoporosis
Supraventricular arrhythmias and hyperlipidaemia
Hypothyroidism and impaired glucose tolerance
Myasthenia gravis and hypothyroidism
Impaired glucose tolerance and hyperlipidaemia
Supraventricular arrhythmias and osteoporosis
Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:
« normal serum free thyroxine and triiodothyronine levels
« with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
Calcium 3.05 mmol/l
Albumin 41 g/l
What is the single most useful test for determining the cause of her hypercalcaemia?
Vitamin D level
Parathyroid hormone levels are useful as malignancy and primary hyperparathyroidism are the two most common causes of hypercalcaemia. A parathyroid hormone that is normal or raised suggests primary hyperparathyroidism.
A 41-year-old man presents with recurrent headaches. These typically occur 2-3 times a day During these episodes his blood pressure is around 210/110 mmHg. Given the likely diagnosis, what is the most appropriate next test?
Phaeochromocytoma: do 24 hr urinary metanephrines, not catecholamines
Three 24 hour collections are needed as some patients have intermittently raised levels
Dapagliflozin is a newer drug for the treatment of diabetes. It is a member of the sodium-glucose transport protein 2 (SGLT2) inhibitor class of drugs.
Which one of the following features is least commonly seen in Gitelman's syndrome?
Gitelman's syndrome: normotension with hypokalaemia
Plasma glucose 1.8 mmol/l
Insulin 15 mg/ml (6-10 mg/ml)
Proinsulin 22% (22-24%)
C-peptide 0.15 nmol/l (0.2-0.4)
What is the most likely diagnosis?
The raised insulin with low c-peptide level points to a diagnosis of insulin abuse.
C-peptide levels would be raised in a patient following sulfonylurea abuse
Hypoglycaemia is defined as a plasma glucose concentration < 2.5 mmol/
If C peptide is undetectable ➡️ Exogenous insulin administration ( as the C peptide is released with endogenous insulin)
nocturnal hypoglycaemia ➡️vivid dreams ➡️ REM sleep disruption ➡️ daytime weakness and somnolence
If the patient's Glasgow Coma Score (GCS) is under 13, then 60-80 ml 20% glucose should be given intravenously.
The most appropriate treatment to correct hypoglycemia is treatment with 10% intravenous dextrose.
Glucagon (1 mg intramuscularly) can be administered if no intravenous access can be obtained.
Glucagon acts mainly on the liver by Activates adenylate cyclase ➡️ increases glycogenolysis and gluconeogenesis
pain in his right thigh. An x-ray is reported as follows:
x-ray right femur Radiolucency of subarticular region suggestive of
Some areas of patchy sclerosis
Bloods tests show:
Alkaline phosphatase 544
Prostate specific antigen 4.4
What is the most appropriate action?
This patient has Paget's disease as evidenced by an isolated rise in ALP and characteristic x-ray changes.
As he has bone pain he should be treated with bisphosphonates.
A PSA of 4.4 ng/ml is probably normal in a 73-year-old man and is certainly not consistent with metastatic prostate
Dynamic pituitary function tests may be used to assess each one of the following, except:
Follicular stimulating hormone
Dynamic pituitary function tests
Used 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
female co abdominal pain with vomiting. She has a past medical history of hypothyroidism and takes thyroxine. she is pyrexial at 37.6°C. Pulse is 110 bpm with a blood pressure of 100/64 mmHg.
Na 131 mmol/l
K 4.9 mmol/l
Urea 8.1 mmol/
Creatinine 110 μmol/l
Glucose 3.3 mmol/l
What treatment should be given first?
Ceftriaxone + benzylpenicillin
This is a typical history of Addison's. Patients may have a history of other autoimmune conditions such as thyroid disorders. Steroids should be given as soon as possible
1. Primary hyperparathyroidism : HIGH PTH, HIGH ca2+, LOW Po4
2. Secondary hyperparathyroidism: HIGH PTH, Normal to Low ca2+, HIGH P04
Tertiary hyperparathyroidism: HIGH PTH, HIGH Ca2+, HIGH P04.
Iron reduces the absorption of thyroxine
initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od
following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks
the therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range
women with established hypothyroidism who become pregnant should have their dose increased 'by at least 25-50 micrograms levothyroxine due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value
Over-replacement can lead to accelerated bone loss and osteoporosis, particularly in women so regular monitoring of TSH is recommended.
Side-effects of thyroxine therapy
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
Drugs interfere with absorption of thyroxine leading to a hypothyroid crisis.
and ferrous sulphate (give at least 2 hours apart)
Which one of the following skin disorders is least associated with hypothyroidism?
Dry, coarse hair
pretibial myxoedema is associated with thyrotoxicosis. There are however case reports of it been found in hypothyroid patients, especially the diffuse non-pitting variety
Skin manifestations of hypothyroidism
dry (anhydrosis), cold, yellowish skin
non-pitting oedema (e.g. hands, face)
dry, coarse scalp hair, loss of lateral aspect of eyebrows
Skin manifestations of hyperthyroidism
erythematous, oedematous lesions above the lateral malleoli No treatment is usually required, Reassurance
But when there is more severe localised pain, then patients may be considered for local use of a potent corticosteroid such as fluocinolone.
Topical fluocinolone is the first line treatment for pretibial myxoedema, but usually only when there is significant pain and discomfort.
Systemic steroids are only rarely used for very severe disease, usually in conjunction with compression bandaging.
thyroid acropachy: clubbing
scalp hair thinning
Pruritus can occur in both hyper- and hypothyroidism
Which of the following is least recognised as a potential complication of acromegaly?
Acromegaly is associated with systemic rather than pulmonary hypertension.
Secondary causes of pulmonary hypertension include COPD, congenital heart disease (Eisenmenger's syndrome), recurrent pulmonary embolism, HIV and sarcoidosis.
A decision is made to start dapagliflozin. Which of the following would you
expect on starting therapy?
Increased blood pressure
Increased serum urate
Increased total cholesterol
Increased total cholesterol
SGLT-2 inhibitors like dapagliflozin promote increased glucose excretion because they inhibit glucose reabsorption in the kidney. This corresponds to a calorie load of 200-400 kcal per day
In some patients, this results in dramatic weight loss, although on average this equates to 1-2%
reduction in weight over 6 months.
SGLT-2 inhibitors are recog cholesterol, (both HDL and LDL), although cardiovascular outcome studies as yet do not
suggest this translates into increased risk of MACE events. In fact, the EMPA-reg study with
empagliflozin demonstrated a reduction in overall mortality nised to increased total
Hypoglycaemia is not a feature of SGLT2 inhibitor use and SGLT-2 inhibitors are associated with
increased urate excretion rather than an increase in serum uric acid
the best choice of sulfonylureas in a patient with renal impairment.?
What is the mechanism of action of mirabegron?
Mirabegron is a beta-3 agonist
Mirabegron is a beta-3 agonist used in the management of urge incontinence if the other drugs such as oxybutynin fail to work or are contraindicated.