Week 12 - Cases 1-3

Question 1

what five clinical features prompt a GP to consider Cushing’s syndrome

Answer 1

• Recent rapid weight gain
• Truncal or central obesity
• Fullness of face or “moon face”
• Increased blood pressure
• Glycosuria (associated with insulin resistance)

Question 2

what are the BMI readings

Answer 2

healthy weight: 18.5–24.9 kg/m2
overweight: 25–29.9 kg/m2
obesity I: 30–34.9 kg/m2
obesity II: 35–39.9 kg/m2
obesity III: 40 kg/m2 or more.

Question 3

what is saxenda

Answer 3

a GLP1 analogue that slows gastric emptying, increased satiety

Question 4

what is the name of Saxenda and when is this a possible treatment on the NHS

Answer 4

Liraglutide (Saxenda) is available on the NHS as a possible treatment for managing weight in adults, if they have: a body mass index (BMI) of at least 35 (or at least 32.5 for some black or ethnic minority people, because their weight-related health risks can be higher at a lower BMI); high blood sugar, which increases their risk of developing diabetes, and high risk of cardiovascular problems such as heart attacks and strokes.

Question 5

when is surgery considered for obese patients

Answer 5

If BMI > 40 or BMI 35-40 with other significant weight-related disease
Tried all non-surgical approaches
Has been or is willing to receive Tier 3 weight management services

Question 6

what kind of obesity is found in Cushing’s

Answer 6

truncal obesity

Question 7

is gynacomastia found in Cushing’s

Answer 7

yes

Question 8

the society of Endocrinology recommend testing for Cushing’s syndrome in what groups

Answer 8

Patients with unusual features for age (e.g., osteoporosis, hypertension)

Patients with multiple and progressive features, particularly those who are more predictive of Cushing’s syndrome

Children with decreasing height percentile and increasing weight

Patients with adrenal incidentaloma compatible with adenoma

Question 9

what are the dexamethasone suppression test results

Answer 9

Normal subject: Reduction in cortisol levels following low-dose dexamethasone.

Cushing’s disease: No reduction in cortisol output after low-dose dexamethasone, but inhibition of cortisol output following high-dose dexamethasone.

Adrenal tumour or ectopic ACTH: No reduction in steroid production after low or high dose dexamethasone.

Question 10

what is cyclical cushing’s

Answer 10

a very rare entity characterised by alternating excess and normal endogenous cortisol secretion and thus can have variable clinical features

if clinical suspicion is high, even if the initial tests are negative, a repeat follow up testing is required. Urinary free cortisol or late-night salivary cortisol are preferred screeing options

Question 11

what are the ACTH dependent cushing syndrome causes

Answer 11

Pituitary Adenoma (Cushing’s Disease) – 65-70%

Ectopic ACTH 5-10% (Bronchial carcinoid commonest)

Unknown source of ACTH <1%

Question 12

what are the ACTH independent causes of cushing syndrome

Answer 12

Adrenal Adenoma – 10-18%

Adrenal Carcinoma 6-8%

Adrenal Hyperplasia

Question 13

what is next test carried out after failure to suppress dexamethasone test

Answer 13

measure ACTH

Question 14

what happens if ACTH-Independent CS (i.e., ACTH <5 pg/mL)

Answer 14

Arrange CT Adrenals to assess adrenal tumour or hyperplasia.

Question 15

what happens if ACTH Dependent CS (pituitary dependent) (i.e., ACTH >20 pg/mL)

Answer 15

Arrange a pituitary MRI; presence of pituitary adenoma > 6mm, is highly consistent with Cushing’s Disease.

Arrange non-invasive tests (High-Dose Dexamethasone Suppression Test (HDDST) and Corticotropin-Releasing Hormone (CRH) stimulation test, if consistent confirms Cushing’s Disease.

Question 16

what happens if Intermediate ACTH (i.e., ACTH 5-20 ng/mL)

Answer 16

Repeat testing and if value remains consistently intermediate then consider Corticotropin-Releasing Hormone test (CRH). The presence of ACTH response suggests ACTH Dependent (Cushing’s Disease), while absence of a response suggest ACTH Independent (Adrenal disease) or ectopic ACTH secretion.

Arrange Inferior Petrosal Sinus Sampling (IPSS) with CRH stimulation for individuals with unclear MRI (lesion <6 mm) or non-concordant HDDST+CRT to distinguish between ectopic ACTH secretion and Cushing’s Disease.

Question 17

what do patients who have a pituitary tumour surgery require

Answer 17

hydrocortisone replacement therapy after the operation

Question 18

what are the consequences of removing all or part of the anterior pituitary gland

Answer 18

The hormones affected and needing replacement could be any of those produced from the anterior pituitary gland:
TSH (Thyroxine)
GH (growth hormone therapy in selected few)
ACTH (hydrocortisone therapy)
FSH/LH (Testosterone or Oestrogen/Progesterone hormone replacement).

Prolactin does not need to be replaced. The posterior pituitary hormones:
(ADH, Endorphins, Oxytocin) do not need replacement as they are not secreted by the pituitary gland but merely stored.

Only, few cases require Desmopressin (synthetic ADH) where ADH secretion is affected because of the damage to posterior pituitary or hypothalamus causing Diabetes Insipidus

Question 19

what are the different types of pituitary tumours

Answer 19

Adenomas arising from different cells are as below:

Gonadotroph adenoma – mostly non-functioning
Thyrotroph adenoma – TSH producing
Corticotroph adenoma – ACTH producing (Cushing’s disease)
Lactotroph adenoma – Prolactin producing
Somatotroph adenoma – GH producing (Acromegaly)

Question 20

what is the name of the cortisol synthesis inhibitor that is used to reduce his adrenal steroid output before going under a bilateral adrenalectomy

Answer 20

Metyrapone

Question 21

what are the hormonal consequences of removing both adrenal glands

Answer 21

no production of glucocorticoid and mineralcorticoid.

he will therefore require glucocorticoid and mineralcorticoid replacement therpay

Question 22

what are the sick day rules in place for people with Cushing’s

Answer 22

requirement to double the dose of glucocorticoids in the event of any medical illness, physical and mental stress, and trauma including surgical procedures

Question 23

LOOK AT SICK DAY RULES ON 1MED.

Question 24

what kind of deficiency is primary adrenal insufficiency associated with

Answer 24

both glucocortocoids and mineralcorticoid deficiency and always needs replacement with cortisol and aldosterone

Question 25

what is the cortisol replacement

Answer 25

hydrocortisone

Question 26

what is the aldosterone replacement

Answer 26

fludrocortisone

Question 27

what test is used to confirm diagnosis of adrenal insufficiency and which test is used to classify the adrenal insufficiency in primary or secondary adrenal failure

Answer 27

Short synacthen test
ACTH test

Question 28

what symptoms may alert you to the presentation of adrenal insufficiency

Answer 28

hyperpigmentation due to elevated levels of ACTH and hence only seen in Addison’s.

electrolyte disturbance and significant postural hypotension are due to lack of mineralcorticoids (due to hypovolaemia and sodium loss) and hence commonly noticed in Addison’s disease

Question 29

how is Addison’s Disease managed?

Answer 29

Life-long cortisol replacement with Hydrocortisone, which remains the main stay.

The patient would need to undergo steroid education, understanding of sick day rules and to double the dose of steroid in various circumstances.

They should be taught how to use parental hydrocortisone in event of emergency, or if unable to take steroid orally. They would need mineralocorticoid replacement using Fludrocortisone.

Question 30

what is primary adrenal insufficiency

Answer 30

Adrenocortical failure due to adrenal disease

Question 31

what is secondary adrenal insufficiency

Answer 31

Adrenocortical failure due to pituitary disease and or lack of ACTH

Question 32

what is tertiary adrenal insufficiency

Answer 32

Adrenocortical failure due to hypothalamus disorder/lack of corticotrophic releasing hormone

Question 33

what is the most common cause of adrenal insufficiency

Answer 33

secondary adrenal insuffiency due to abrupt withdrawal of chronic glucocorticoid therapy or pituitary disease

Question 34

what are the other , less common reasons for Addison’s disease

Answer 34

Infections (Tuberculosis, HIV/AIDS)
Infiltration (Malignancy, Amyloid, Lymphoma, haemochromatosis)
Haemorrhage/Infarction
Surgical removal (bilateral adrenalectomy)
Medications (metyrapone, ketoconazole)
Adrenal leukodystrophy (rare)

Question 35

what is Addisonian crisis

Answer 35

patients with adrenal insufficiency can present with acute crisis leading to circulatory shock and severe hypotension, hyponatraemia, hyperkalaemia, metabolic acidosis, and possible hypoglycaemia.

Question 36

what are the precipitant factors of addisonian crisis

Answer 36

intercurrent disease. surgery, or infection

Question 37

what is the management of addisonian crisis

Answer 37

1. correcting the volume depletion
2. replacing glucocorticoids parentally
3. correcting metabolic abnormalities
4. identifying the underlying cause
5. patient education before discharge, to prevent further occurrence.

Question 38

what are the four distinct regions of the adrenal gland

Answer 38

zona glomerulosa

zona fasiculata

zona reticularis

medulla

Question 39

hormones produced by the adrenal glands are synthesised from what

Answer 39

cholesterol

Question 40

how does metyrapone work

Answer 40

it is a glucocortcoid synthesis inhibitor.

it works by inhibiting 11-beta hydroxylase, thereby inhibiting synthesis of cortisol from deoxycortisol and the synthesis of corticosterone from deoxycorticosterone in the adrenal gland

Question 41

what is the mechanism by which ramipril causes a cough

Answer 41

ACE inhibitors can lead to an increase in a substance called bradykinin. This can irritate the airways, triggering inflammation and coughing.

Question 42

what are the causes of hypervolaemic hyponatraemia

Answer 42

heart failure
cirrhosis
chronic kidney disease
nephrotic syndrome

Question 43

what are the euvolemic causes of hyponatraemia

Answer 43

glucocorticoid deficiency
hypothyroidism
SIADH
cancer

Question 44

what are the hypovolemic causes of hyponatraemia

Answer 44

diuretic therapy
mineralcorticoid deficiency
burns
salt wasting neuropathy

Question 45

what is the unifying diagnosis that may like a symptom like a cough to low sodium

Answer 45

This patient is a smoker, and has had a cough for over 4 weeks. The concern is that they could have a lung cancer causing Syndrome of Inappropriate ADH (SIADH).

Question 46

what is diabetes insipidus

Answer 46

This is a rare condition.

This is where either too little vasopressin is produced by the pituitary – ‘cranial diabetes insipidus’ or the kidney becomes insensitive to vasopressin and does not make aquaporin channels and reabsorb water from the collecting ducts – ‘nephrogenic diabetes insipidus.

In these conditions large quantities of dilute urine are produced – polyuria – and to compensate people drink large quantities of water – polydipsia.

If people are unable to drink water they will develop high body sodium levels, hypernatraemia, and become dehydrated. This is the basis of the water restriction test to diagnose diabetes insipidus.

Question 47

what is the clinical approach to hypernatraemia

Answer 47

This is more unusual and is only seen associated with dehydration where the person has been unable to access water. This usually occurs in elderly patients who have dementia which has impaired their sense of thirst or patients in medically induced comas on ITU. It can also occur if you are in a hot weather (e.g., a desert) and do not have enough water.

Question 48

what is mild nephritic syndrome

Answer 48

Mild nephritic – Disorders resulting in a mild nephritic sediment are generally associated with inflammatory lesions of glomeruli on light microscopy (focal glomerulonephritis). The urinalysis reveals red cells (which often have a dysmorphic appearance), occasionally red cell casts, and mild proteinuria (usually less than 1.5 g/day). The findings of more advanced disease are usually absent, such as heavy proteinuria, oedema, hypertension, and kidney function impairment. These patients often present with asymptomatic haematuria and proteinuria discovered on routine examination or, occasionally, with episodes of gross haematuria.

Question 49

what is severe nephirtic

Answer 49

Severe nephritic – The urinalysis in diffuse glomerulonephritis is similar to focal disease, but heavy proteinuria (which may be in the nephrotic range), oedema, hypertension, and/or kidney function impairment may be observed. Diffuse glomerulonephritis affects most or all of the glomeruli.

Question 50

what is nephrotic syndrome

Answer 50

Nephrotic – The nephrotic sediment is associated with heavy proteinuria and lipiduria, but few cells or casts and is typically considered bland. The term “nephrotic syndrome” refers to a distinct constellation of clinical and laboratory features of kidney disease. It is specifically defined by the presence of heavy proteinuria (protein excretion greater than 3.5 g/24 hours), hypoalbuminemia (less than 3.5 g/dL), and peripheral oedema. Hyperlipidemia and thrombotic disease are also frequently observed.

Question 51

what is the gold standard investigation for diagnosing nephrotic and nephritic syndrome

Answer 51

renal biopsy

Question 52

what is the main reason for ADPKD

Answer 52

Mutations in PKD1 (on chromosome 16) are responsible for 85% of cases, with mutations in PKD2 (on chromosome 4) accounting for the remainder. These genetic abnormalities are distinct from the autosomal recessive form of polycystic disease (due to mutations in the PKHD1 gene on chromosome 6p21.1-p12), which is often lethal in early life.

PKD1 encodes polycystin 1, involved in cell–cell and/or cell–matrix interactions. PKD2 encodes polycystin 2, which functions as a calcium ion channel. The polycystin complex occurs in cilia, responsible for sensing flow in the tubule. Disruption of the polycystin pathway results in reduced cytoplasmic calcium, which, in principal cells of the collecting duct, causes defective ciliary signalling and disoriented cell division, leading to cyst formation. Extra-renal manifestations include an increased level of intracranial aneurysms and polycystic liver disease, which can be severe and associated with significant morbidity.

Question 53

what are the presenting symptoms of ADPKD

Answer 53

Loin pain and/or haematuria from haemorrhage into a cyst, cyst infection or urinary tract stone formation

Loin or abdominal discomfort as the size of the kidneys increases

Subarachnoid haemorrhage associated with berry aneurysm rupture

Complications of hypertension

Complications of associated liver cysts (occur in around 50%)

Symptoms of uraemia and/or anaemia associated with CKD

Question 54

what are the two potential strategies to treat ADPKD

Answer 54

Vasopressin receptor antagonists, which act by inhibiting cAMP in principal cells, reduce cyst growth and slow the rate of progression of renal failure; they have been approved for use in patients with CKD (eGFR>30 ml/min) with rapid disease progression. Reversible liver toxicity requires close monitoring.

In the HALT-PKD study A, patients with early PKD and eGFR >60 mL/min, when randomized to a low blood pressure group (95/60–110/75 mmHg), had slower annualized increase in total kidney volume and lower albuminuria and left ventricular mass index, compared to the standard blood pressure group (120/70–130/80 mmHg).

Question 55

A 50 year old lady is diagnosed with Cushings disease and listed for pituitary surgery. Which of the following is the most appropriate pre-operative treatment to reduce cortisol production?

Answer 55

Metyrapone

Question 56

A 75 year old gentleman is referred to endocrinology with a 6 month history of increasing central obesity, skin bruising and resistant hypertension. He has plethoric cheeks and rounded face. Which of the following is a first line diagnostic test for Cushings?

Answer 56

Overnight Dexamethasone suppression test

Question 57

65 year old man presents to clinic with a chronic cough and several episodes of haemoptysis. He has a 40 pack year smoking history and finger clubbing. He reports difficulty rising from a seated position and you note purple striae on his skin. Which of the following is the most likely cause of his skin changes?

Answer 57

Ectopic ACTH release

Question 58

Which test would allow discrimination between a pituitary and ectopic source of excess ACTH?

Answer 58

Inferior Petrosal Sinus Sampling

Question 59

25-year-old man developed sudden onset of leg swelling and noticed increased body weight. His urine dipstick showed +++ protein. Which of the following is not a common manifestation of nephrotic syndrome?

Answer 59

Oliguria

Question 60

Which of the following is an ultrasound diagnostic criterion for adult polycystic kidney disease with a positive family history?

Answer 60

15–29years: ≥3 cysts (Bilateral)

Question 61

A 22-year-old woman, known to have systemic lupus erythematosus, presented with an acute kidney injury, with blood and protein on urine dip stick. Which is the diagnostic investigation most likely to guide management?

Answer 61

Renal biopsy