High-Yield Endocrinology

Acromegaly

• Pathophysiology:
Excess GH (usually from pituitary adenoma) → increased IGF-1 →
tissue overgrowth.
• Symptoms:
Coarse facial features, enlarged hands/feet, headaches, visual field
defects, hypertension.
• Treatment & Rationale:
1. Transsphenoidal surgery – first-line to remove adenoma.
2. Somatostatin analogues (e.g., octreotide) – suppress GH secretion.
3. Pegvisomant – GH receptor antagonist for resistant cases.
4. Radiotherapy – adjunct if surgery/injections fail.
 Cushing’s Syndrome vs Disease

• Pathophysiology:
Cushing’s syndrome: Excess cortisol from various causes.
Cushing’s disease: ACTH-secreting pituitary adenoma → adrenal
cortisol excess.
• Symptoms:
Central obesity, moon face, purple striae, easy bruising, proximal
weakness, osteoporosis, hypertension, diabetes.
• Treatment & Rationale:
1. Surgery – remove ACTH or adrenal tumour (primary treatment).
2. Ketoconazole/metyrapone – inhibit cortisol synthesis (used if
surgery is delayed/contraindicated).
3. Mifepristone – glucocorticoid receptor blocker (in select cases).
 Cushings
• What is it?
Cushing’s syndrome = too much cortisol in the body for a prolonged
time.
• Causes fall into 3 main categories:
• Iatrogenic (most common)
→ You’re giving corticosteroids to the patient (e.g. for asthma, lupus)
• ACTH-dependent
– Cushing’s disease → a pituitary tumour produces too much ACTH
– Ectopic ACTH → a non-pituitary tumour (often small cell lung cancer)
produces ACTH
• ACTH-independent
– Adrenal tumour (adenoma or carcinoma) produces excess cortisol directly
 Low dose
• Checks if hypercortisolism or not
 High dose dexamethasone suppression test

At the hypothalamus, dexamethasone inhibits the release of corticotropin-releasing hormone

(CRH).
At the anterior pituitary, dexamethasone reduces secretion of adrenocorticotropic hormone
(ACTH).

Cortisol Suppression ACTH Level Likely Diagnosis

Cushing’s disease (pituitary
Suppressed Normal or high
adenoma)
Not suppressed Elevated Ectopic ACTH secretion
Adrenal adenoma or
Not Suppressed Low
carcinoma
• Na⁺ reabsorption increases → urine becomes
more negatively charged
• To balance charges, the kidney secretes
positively charged H⁺ ions into the urine
• Loss of H⁺ from blood → blood becomes more
alkaline → metabolic alkalosis
 Type 1 Diabetes Mellitus

• Pathophysiology:
Autoimmune destruction of pancreatic beta cells → absolute
insulin deficiency.
• Symptoms:
Polyuria, polydipsia, weight loss, fatigue, DKA.
• Treatment & Rationale:
1. Insulin therapy – essential as patient lacks endogenous insulin.
- Basal-bolus regimen (mimics physiologic insulin release).
- CSII (pump) in selected patients.
2. Education – carb counting, blood glucose monitoring, sick day
rules.
 Type 2 Diabetes Mellitus

• Pathophysiology:
Insulin resistance and progressive beta-cell dysfunction.
• Symptoms:
Often asymptomatic; polyuria, fatigue, recurrent infections.
• Treatment & Rationale:
1. Metformin – reduces hepatic gluconeogenesis, improves insulin
sensitivity.
2. SGLT2 inhibitors (e.g., dapagliflozin) – promote glycosuria, improve CV
outcomes.
3. GLP-1 receptor agonists (e.g., semaglutide) – enhance insulin, promote
weight loss.
4. DPP-4 inhibitors (e.g., sitagliptin) – increase endogenous incretin.
5. Insulin – used when oral agents fail or in acute illness.
 Hyperthyroidism (including Subacute)

• Pathophysiology:
Graves’ disease: Autoimmune stimulation of TSH receptor.
Toxic multinodular goitre or adenoma: autonomous thyroid hormone production.
Subacute (de Quervain’s): Post-viral inflammation → hormone release.
• Symptoms:
Weight loss, tremor, palpitations, heat intolerance, anxiety, goitre, eye disease
(Graves’).
• Treatment & Rationale:
1. Carbimazole – inhibits thyroid hormone synthesis.
2. Propylthiouracil – used in pregnancy (1st trimester).
3. Beta-blockers – control adrenergic symptoms.
4. Radioactive iodine – definitive in Graves’/TMNG (not in pregnancy).
5. Surgery – large goitre or ophthalmopathy.
6. Subacute – NSAIDs/steroids for inflammation (it is transient)
 Hypothyroidism

• Pathophysiology:
Hashimoto’s thyroiditis (autoimmune), post-surgical, or post-
radioiodine.
• Symptoms:
Fatigue, cold intolerance, weight gain, dry skin, constipation,
bradycardia.
• Treatment & Rationale:
1. Levothyroxine – replaces deficient T4.
- Titrated using TSH monitoring.
- Taken on empty stomach, away from calcium/iron.
 Parathyroid Disorders

• Pathophysiology:
Primary hyperparathyroidism – usually due to adenoma → ↑ PTH →
hypercalcemia.
Secondary – due to CKD or vit D deficiency.
Hypoparathyroidism – often post-surgical or autoimmune.
• Symptoms:
Hyper: 'Bones, stones, groans, moans.'
Hypo: Tetany, Chvostek's/Trousseau's signs, seizures.
• Treatment & Rationale:
1. Hyper – parathyroidectomy (definitive), bisphosphonates or
cinacalcet for symptom control.
2. Hypo – calcium and vitamin D supplementation.
 What does PTH do
• 1. Calcium (Ca²⁺)
– PTH raises serum calcium by:
• Increasing bone resorption → releases calcium (and phosphate) into the blood.
• Increasing renal tubular reabsorption of calcium → less calcium lost in urine.
• Increasing activation of vitamin D (calcitriol) in kidneys → increases intestinal absorption of calcium.
– In primary hyperparathyroidism:
→ Calcium is high (hypercalcaemia).
– In secondary hyperparathyroidism (e.g. CKD):
→ Calcium is low or normal because of underlying causes like vitamin D deficiency or phosphate retention.
– In tertiary hyperparathyroidism:
→ Calcium is high again due to autonomous PTH secretion.
• 2. Phosphate (PO4³⁻)
– PTH decreases serum phosphate by:
• Reducing phosphate reabsorption in the proximal renal tubules → increased phosphate excretion (phosphaturia).
– In primary hyperparathyroidism:
→ Phosphate is low (hypophosphataemia).
– In secondary hyperparathyroidism (especially CKD):
→ Phosphate is high (hyperphosphataemia) because kidneys fail to excrete phosphate properly despite high PTH.
– In tertiary hyperparathyroidism:
→ Phosphate can remain high or normalize, but kidney dysfunction often means phosphate stays elevated.
• 3. Alkaline Phosphatase (ALP)
– ALP is an enzyme produced by osteoblasts during bone formation.
– In hyperparathyroidism, PTH increases bone turnover (both resorption and formation).
– This leads to increased activity of osteoblasts trying to rebuild bone → ALP levels rise.
– So, ALP is elevated in all types of hyperparathyroidism, reflecting high bone remodeling.
• 4. Vitamin D
– PTH stimulates conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol) in kidneys.
– However:
• In primary hyperparathyroidism, vitamin D levels are often normal or low (low vitamin D can worsen hyperparathyroidism).
• In secondary hyperparathyroidism (especially CKD), vitamin D activation is impaired → low active vitamin D levels, contributing to hypocalcaemia and increased
 Why can PTH be normal in
hyperparathyroidism
• When Ca++ is high PTH should be suppressed
• If Ca++ is high and PTH is normal this is not
normal
• In hypercalcaemia PTH being normal is
abnormally high
 SIADH

• Pathophysiology:
Excess ADH → water retention → dilutional hyponatremia.
• Symptoms:
Confusion, seizures, nausea, cerebral edema (if severe).
• Treatment & Rationale:
1. Fluid restriction – first-line to reduce free water intake.
2. Tolvaptan – vasopressin receptor antagonist (select
cases).
3. Hypertonic saline – in severe symptomatic hyponatremia.
4. Treat underlying cause (e.g., malignancy, CNS pathology).
 SIADH pathophysiolgoy
• Syndrome of Inappropriate Antidiuretic Hormone secretion
(SIADH) is characterised by excess ADH release despite normal
or low plasma osmolality.
• Excess ADH causes increased water reabsorption in the
collecting ducts of the kidney, leading to water retention.
• This results in dilutional hyponatraemia with:
• Low serum osmolality
• Inappropriately concentrated urine (urine osmolality >100
mOsm/kg)
• Euvolaemia clinically (no oedema or dehydration)
• Key feature: Impaired water excretion despite low plasma
osmolality.
 Diabetes Insipidus

• Pathophysiology:
Central DI: deficiency of ADH.
Nephrogenic DI: renal insensitivity to ADH.
• Symptoms:
Polyuria, polydipsia, dehydration, hypernatremia.
• Treatment & Rationale:
1. Central – desmopressin (synthetic ADH).
2. Nephrogenic – thiazide diuretics, low salt/protein
diet to reduce urine output.
 Water deprivation test
Urine
Osmolality Response to
Diagnosis Serum Sodium Comments
during Desmopressin
Deprivation

Adequate
Increases (>600
Normal N/A Normal endogenous
mOsm/kg)
ADH secretion

Increases May rise ADH deficiency

Remains low
Central DI significantly (hypernatremia (pituitary
(<300 mOsm/kg)
(>50%) risk) problem)

No significant Kidney
Nephrogenic Remains low
increase May rise unresponsive to
DI (<300 mOsm/kg)
(<10%) ADH

Excess water
Primary Gradual increase Minimal or no Usually
intake
Polydipsia (>300 mOsm/kg) change low/normal
suppresses ADH
 Causes of DI
• Malignancies: Small cell lung carcinoma (most
classic)
• CNS disorders: Stroke, trauma, infections
(meningitis)
• Pulmonary diseases: Pneumonia, TB, abscess
• Drugs: SSRIs, carbamazepine,
cyclophosphamide, NSAIDs
• Other: Postoperative states, HIV, hereditary
causes
 Case 1
• A 45-year-old man presents with coarse facial
features, large hands, and a deepened voice.
Which hormone is most likely elevated?
A) Prolactin
B) Growth Hormone
C) Cortisol
D) Thyroid Stimulating Hormone
E) Parathyroid Hormone
 Case 2
• A patient with suspected Cushing’s syndrome has
a low-dose dexamethasone suppression test
showing no suppression of cortisol. Plasma ACTH
is elevated. What is the next best test to localize
the source?
A) High-dose dexamethasone suppression test
B) Serum aldosterone
C) MRI of adrenal glands
D) Serum TSH
E) Insulin tolerance test
 Case 3
• Question 3
• Which of the following drugs used in Type 2
diabetes can lead to an increased chance of
amputation?
A) Metformin
B) Sulfonylureas
C) SGLT2 inhibitors
D) DPP-4 inhibitors
E) Thiazolidinediones
 Case 4
• A patient with hyperthyroidism presents with
fever, neck pain, and a tender thyroid gland.
Which is the most likely diagnosis?
A) Graves’ disease
B) Subacute (de Quervain’s) thyroiditis
C) Hashimoto’s thyroiditis
D) Toxic multinodular goiter
E) Thyroid cancer
 Case 5
• Which of the following blood test patterns is
most consistent with primary
hyperparathyroidism?
A) High calcium, low phosphate, high PTH
B) Low calcium, high phosphate, high PTH
C) High calcium, high phosphate, low PTH
D) Low calcium, low phosphate, low PTH
E) Normal calcium, normal phosphate, low
PTH
 Case 6
• A 35-year-old woman with acromegaly is scheduled for
transsphenoidal surgery. Preoperative testing reveals
elevated IGF-1 and inadequate GH suppression during
an oral glucose tolerance test. Which of the following
drugs is the best initial medical treatment to reduce
tumor size and hormone secretion before surgery?
A) Cabergoline
B) Octreotide
C) Bromocriptine
D) Levothyroxine
E) Ketoconazole
 Case 7
• A patient with suspected Cushing’s syndrome has a
midnight serum cortisol of 220 nmol/L (normal <50
nmol/L) and a 24-hour urinary free cortisol elevated
twice above the upper limit. Plasma ACTH is low.
Which of the following is the most likely diagnosis?
A) Pituitary adenoma
B) Ectopic ACTH secretion
C) Adrenal adenoma
D) Exogenous corticosteroid use
E) Pseudo-Cushing’s syndrome
 Case 8
• A 62-year-old patient with T2DM develops foot ulcers
and chronic kidney disease (eGFR 25). He is on
metformin, gliclazide, and empagliflozin. Which of the
following changes is MOST appropriate in his
management?
A) Add pioglitazone to improve insulin sensitivity
B) Stop metformin due to worsening kidney function
C) Increase gliclazide dose to control glucose
D) Stop empagliflozin due to risk of diabetic
ketoacidosis
E) Start insulin immediately
 Case 9
• Question 14
• A 50-year-old woman with stage 4 chronic kidney disease has
persistently elevated parathyroid hormone levels despite
normal serum calcium. Which of the following best explains
this finding?
• A) Primary hyperparathyroidism with normocalcaemia
B) Secondary hyperparathyroidism due to phosphate
retention and decreased calcitriol production
C) Tertiary hyperparathyroidism due to autonomous
parathyroid hyperplasia
D) Vitamin D intoxication causing PTH suppression
E) Parathyroid carcinoma with normal calcium levels
 Case 10
• A 65-year-old woman presents with gradually worsening
palpitations, weight loss, and heat intolerance over
several months. On examination, she has an irregularly
enlarged thyroid gland and no eye signs or pretibial
myxedema. Thyroid function tests show suppressed TSH
and elevated free T4. What is the most likely diagnosis?
• A) Graves’ disease
B) Toxic multinodular goitre
C) Subacute thyroiditis
D) Hashimoto’s thyroiditis
E) Thyroid cancer