Endocrinology

Question 1

What is the commonest cause of thyrotoxicosis?

Answer 1

Graves disease

It is typically seen in women aged 30-50 years.

Features
typical features of thyrotoxicosis
specific signs limited to Grave’s (see below)

Features seen in Graves’ but not in other causes of thyrotoxicosis
eye signs (30% of patients)
exophthalmos
ophthalmoplegia
pretibial myxoedema
thyroid acropachy, a triad of:
digital clubbing
soft tissue swelling of the hands and feet
periosteal new bone formation

Question 2

Auto- antibodies specific to graves disease?

Answer 2

Autoantibodies
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)

Thyroid scintigraphy
diffuse, homogenous, increased uptake of radioactive iodine

Question 3

Management of DM

Answer 3

Always start with life style changes/ dietary advice
HbA1c target 48

Drug therapy

*** 1st line
(does the pt have high/ established CVD risk/ CHF?)
If no- Metformin
If yes- Metformin, once established on metformin, add SGLT2 inhibitor

What to do if Metformin not tolerated due to GI side effects or if metformin is contraindicated
Again, does pt have high CVD risk
If no- DPP-4 inhibitor or pioglitazone or sulfonylurea (SGLT 2 inhibitor if criteria are met)
If yes- SGLT2 monotherapy

HbA1c for pt with lifestyle + metformin 48
HbA1c for lifestyle with any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53

Further drug therapy if HbA1c targets not met

Second-line therapy

Dual therapy - add one of the following:
metformin + DPP-4 inhibitor
metformin + pioglitazone
metformin + sulfonylurea
metformin + SGLT-2 inhibitor (if NICE criteria met)

Third-line therapy

If a patient does not achieve control on dual therapy then the following options are possible:
metformin + DPP-4 inhibitor + sulfonylurea
metformin + pioglitazone + sulfonylurea
metformin + (pioglitazone or sulfonylurea or DPP-4 inhibitor) + SGLT-2 if certain NICE criteria are met
insulin-based treatment

Further therapy

If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic:
BMI ≥ 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months

GLP-1 mimetics should only be added to insulin under specialist care

Starting insulin
metformin should be continued. In terms of other drugs NICE advice: ‘Review the continued need for other blood glucose-lowering therapies’
NICE recommend starting with human NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need

Question 4

Pioglitazone
Class and SE

Answer 4

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)

Question 5

Acromegaly
Cause
Features
Complication

Answer 5

In acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.

Features
coarse facial appearance, spade-like hands, increase in shoe size
large tongue, prognathism, interdental spaces
excessive sweating and oily skin: caused by sweat gland hypertrophy
features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases → galactorrhoea
6% of patients have MEN-1

Complications
hypertension
diabetes (>10%)
cardiomyopathy
colorectal cancer

Question 6

Causes of hypercalcemia

Answer 6

Two conditions account for 90% of cases of hypercalcaemia:

1. Primary hyperparathyroidism: commonest in non-hospitalised pt
2. Malignancy: the commonest in hospitalised pts. Due to many things;
   PTHrP from the tumour e.g. squamous cell lung cancer
   bone metastases
   myeloma,: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells

Other causes include
sarcoidosis/ TB/ histoplasmosis (granulomatous dx)
vitamin D intoxication
acromegaly
thyrotoxicosis
Milk-alkali syndrome
drugs: thiazides, calcium containing antacids
dehydration
Addison’s disease
Paget’s disease of the bone - hypercalcaemia may occur with prolonged immobilisation

Question 7

Drug causes of raised prolactin

Answer 7

metoclopramide, domperidone
phenothiazines (antipsychotics Chlorpromazine)
haloperidol
very rare: SSRIs, opioids