ENDO

DIABETES
A 36-year-old manager spends long hours on his job and used to consume soft drinks and
junk food. He is a heavy smoker and drinks alcohol regularly. He complains of tiredness and
sleepiness in the evenings. He is 170 cm in height and weighs 85 Kg. His fasting blood sugar
is 16.6 mM/L.
1. Calculate his Body mass index[BMI}. (2 marks)
85kg/(1.7m x 1.7m)= 29.41 kg/m2
2. List FOUR commonly used oral hypoglycemic agents giving one example of each (4
marks)
Sulfonylureas - glimepiride, glipizide, glyburide, tolazamide, tolbutamide
Biguanides - metformin.
Thiazolidinediones (Tzd) - pioglitazone, rosiglitazone.
Alpha-glucosidase inhibitors – Acarbose, Miglitol.
Meglitinides - nateglinide.
Combination of sulfonylureas plus metformin - known by generic names of the two drugs
3. Advise which oral antidiabetic drug to take and when to take with regard to meals. (2
marks)
Metformin, take with meal or immediately after meal.
4. State the mechanism of action of the drug given above. (2 Marks)
MOA of metformin -Any two
CNS-reduce appetite
GI-reduces glucose absorption
Liver-inhibits hepatic gluconeogenesis and lipogenesis
increases insulin receptor number or affinity
reduces insulin resistance
increases glucose uptake by muscle in the presence of insulin
DIABETIC KETOACIDOSIS
A diabetic woman took her insulin dose every morning. One day, she came in with
hyperventilation and tachycardia. Her blood sugar is 480 mg/ml. Upon urinalysis, ketone
bodies were found in her urine.
A. Explain the pathophysiology behind this woman's condition. (4m)
B. What is the acid base disorder? What will happen to the anion gap? (2m)
C. Describe the immediate treatment for this patient. (4m)
HYPERTHYROIDISM
A 35 year old woman is admitted to the hospital with a lump in front of her neck which was
gradually increasing in size for the past one year. She has lost about 8 kg of her body weight
during the past 3 months. Her appetite is normal. She has noticed increased sweating and
palpitation during the past 4 months. The lump in front of her neck moves up when she is
asked to swallow. Primary hyperthyroidism is diagnosed and patient is treated with
carbimazole and propranolol.

a. Explain the anatomical basis for moving up of the thyroid swelling with swallowing.
Thyroid gland is surrounded by the pre-tracheal fascia which is attached to the thyroid
cartilage. During swallowing, thyroid cartilage moves up thus moving thyroid gland
(2 marks)

b. Explain the physiological basis for her palpitations

Thyroid hormones normally increase heart rate and the force of ventricular contraction by (1)
direct stimulation (2) potentiation of catecholamine (adrenaline, noradrenaline) action on the
SA node and the myocardium through increasing the number and affinity of beta-adrenergic
receptors to catecholamines. Excessive thyroid hormone action in thyrotoxicosis leads to
increased heart rate and strong heart beat to which the woman is aware of (palpitations)
(0.5x6 = 3 marks)

c. Name TWO (2) laboratory investications which confirm her diagnosis. Explain how
the diagnosis is made based on the results.
Laboratory investigations Interpretation of the tests
Blood TSH levels TSH levels are reduced in primary hyperthyroidism due to
negative feedback suppression by raised T3 & T4
Plasma T3 and T4 (Free T3, T3, T4 levels are increased with high gland activity
T4)
(smth smth) antibodies High titres suggests Graves disease
Thyroid stimulating Increased levels suggests primary hyperthyroidism
immunoglobulins
Radioactive iodine uptake on Diffuse high uptake suggests thyrotoxicosis
scintigraphy

(3 marks)
 d. Explain the mechanism of action of the two drugs used

Answer :
Name of the Mechanism of action
Drug
Carbimazole  Inhibit thyroid hormone synthesis by blocking oxidation,
organification and coupling of iodine in the thyroid gland
Propranolol  Inhibition of B-adrenoreceptors (clinical improvement of
hyperthyroid symptoms)
 Inhibit peripheral conversion of T4 to T3. (either one)

(2 marks)
CUSHING’S SYNDROME
A 35-year-old woman presented with low back pain and generalised muscle weakness.
Physical examination showed purple/pink stretch marks on her arms, abdomen and thighs.
A 24-hour urinary free cortisol assay and low dose dexamethasone suppression test were
positive. Following this, a high dose dexamethasone test was administered. The results
showed that the levels of urinary cortisol remained high and the serum ACTH levels were
low. A diagnosis of Cushing syndrome due to adrenal adenoma was made.

6A. Explain the pathophysiology of low back pain, muscle weakness and stretch marks in
this patient. (4 marks)

Low back pain - excessive cortisol inhibits bone formation which may increase bone
demineralisation leading to premature osteoporosis and fracture of the vertebrae in the
lumbar region. (1 mark for each underlined answer)

Muscle weakness - high cortisol increases proteolysis, which reduces muscle mass
especially of the proximal limb muscles (1 mark)

Stretch marks - Cortisol decreases collagen synthesis and leads to thin skin. (1 mark)

6B. Name the zone of the adrenal cortex affected in this patient. Describe its histological
features. (3 marks)

***Already raised at feedback session: ANSWER GIVEN HERE IS WRONG.

It should be zona fasciculata instead. Just putting this down anyway to learn
about histology of glomerulosa.

6C. Explain how the findings of the laboratory tests lead to the above diagnosis. (3
marks)

Cushing syndrome due to adrenal adenoma the high dose of dexamethasone (analog of
cortisol) suppressed the pituitary gland, which accounts for the low ACTH detected. Despite
the low ACTH, the adrenal gland continued to secrete cortisol, which accounts for the high
levels of urinary cortisol detected. The high secretion of cortisol could be due to the tumour
of the adrenal gland.
ADRENAL ADENOMA
A 30-year-old woman presented with complaints of weight gain over the past 6 months. On
physical examination, she had a moon face, facial plethora and ecchymosis of the extremities.
The circadian rhythm of plasma cortisol disappeared. Elevated urinary free cortisol levels
were noted, and the ACTH level was undetectable. A 48-hour low-dose dexamethasone test
was performed and later a high-dose dexamethasone suppression test was also performed.
The blood test results showed elevated glucose levels. Adrenal contrast-enhanced computed
tomography (CT) revealed bilateral, round and smooth-contoured nodules.
a. What is the most likely diagnosis in this patient?
List TWO (2) other parts of the body there could be central deposition of fat in this patient.
[1+1]
 ACTH-independent adrenal hyperfunction due to an adrenal tumour / adrenal
adenoma
 Trunk (truncal obesity), posterior neck and back (buffalo hump)
b. Describe the circadian rhythm of cortisol secretion.
Explain the most likely cause for the disappearance of the circadian rhythm. [2+1]
 Very low or undetectable cortisol levels at mid night that build up overnight to peak
in the morning. Cortisol leves then decline slowly throughout the day.
 Hypersecretion of cortisol from adrenal tumour not regulated by the main circadian
oscillator.
c. Explain the reason for the high glucose level detected in this patient. [3]
High cortisol levels enhance gluconeogenesis in the liver. However, cortisol inhibits glucose
uptake by extrahepatic tissues (eg: muscle and adipose), sparing the glucose for the brain and
heart. This results in the rise of blood glucose levels (i.e. hyperglycemia).
d. Describe the likely histopathological findings of the adrenal nodules seen in the CT
scan of this patient. [2]
Adrenal adenomas show clear, lipied-laden (fasciculate type) cells arranged in sheets/nests.
These are often interspersed with clusters of compact, lipid-depleted eosinophilic (reticularis
type) cells.
HYPOTHYROIDISM
A 45-year-old woman presents with fatigue, constipation, menorrhagia and weight gain for
the past six months. On physical examination, there is no pallor. The skin is cool, dry, and
rough. The pulse rate is 50 bpm and examination of thyroid gland shows mild diffuse
enlargement with a rubbery consistency. Laboratory investigations reveals hypothyroidism
and Hashimoto thyroiditis is suspected.
6A. State the TWO types of endocrine cells in the normal thyroid gland. Describe the
microscopic arrangement of the cells stated within the normal thyroid gland.
(2 marks)
Follicular cells: arranged as cells lining the follicles
Para follicular cells: arranged as group of cells in the space between follicles
6B.
(i) Describe the effect of thyroxine on lipid metabolism. (2 marks)
(ii) Explain the biochemical basis for weight gain in this patient. (1 mark)
Thyroxine decreases the lipid storage (increase lipolysis) by mobilizing it from adipose
tissues. The mobilized lipid is converted into free atty acids and transported by blood.
In hypothyroidism, decrease in thyroxine, fat deposition, ↑ body weight.
6C. Name ONE antibody used to confirm the diagnosis of the disease in this patient. (1
mark)
Antibody against thyroid peroxidase
Antibody against thyroglobulin
6D. Explain the immunopathogenesis of hypothyroidism in this patient.(4 marks)
Breakdown in self-tolerance to thyroid auto antigen leads to activation of the immune system.
Induction of thyroid autoimmunity leads to formation of auto antibodies which destroys
thyrocytes.
Thyroid immune activation also activates CD8+ cytotoxic T cells and CD4+ helper T cells to
produce cytokines which further leads to death of thyrocytes.
Replacement of the thyroid parenchyma by mononuclear cell infiltration and fibrosis leads to
reduced secretion of thyroid hormones.
PITUITARY ADENOMA
A man complains about being unable to see the sides of his vision. It is found that there is an
increase in the number of somatotrophs in his pituitary gland.
A. What is the loss of vision called? Explain the pathophysiology behind his loss of vision.
(4m)
Bitemporal hemianopia. When the adenoma grows it tends to compress the neighbouring
structures. When the tumor presses upwards from the sella turcica on the bottom of the optic
chiasm, the optic chiasm is compressed and the patient experiences bitemporal hemianopia
B. What is the hormone affected? Explain how this would affect his glucose tolerance status.
(3m)
Growth hormone. Growth hormons induces liver gluconeogenesis, there will be elevated
insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose.
The patient will present with impaired glucose tolerance.
C. Explain the gross pathology of the pituitary gland in this man (3m)
Soft, well circumscribed lesion, confined to the sella turcica. Larger lesion extend into the
suprasellar region compress the optic chiasm and adjacent structures such as some cranial
nerves. **