• Structured long-answer and short-note headings
• Conceptual pathophysiology linked to clinical findings
• Investigation hierarchy, diagnostic criteria, differentials, and management
• Emergency versus definitive treatment
• Viva questions, MCQs, mnemonics, flowcharts, and revision tables
• Relevant ECG, imaging, ABG, pharmacology, and guideline points where appropriate

• Acute coronary syndrome
• Heart failure
• COPD or bronchial asthma
• DKA
• Cirrhosis with ascites
• AKI/CKD
• Stroke
• Tuberculosis
• Anemia
• Rheumatoid arthritis/SLE

1. Acromegaly and gigantism
   • GH excess and its causes
   • Clinical recognition, IGF-1 and glucose-suppression testing
   • MRI, visual-field assessment, treatment with surgery, somatostatin analogues, pegvisomant, and radiotherapy
   • Cardiometabolic, respiratory, colonic, and pituitary complications
2. Hyperprolactinemia
   • Physiological, drug-induced, stalk-related, and prolactinoma causes
   • Galactorrhea, menstrual dysfunction, infertility, hypogonadism, and mass effects
   • Correct interpretation of prolactin level, pregnancy test, thyroid tests, macroprolactin, and pituitary MRI
   • Dopamine agonist treatment, particularly cabergoline
3. Hypopituitarism and Sheehan syndrome
   • Causes and patterns of anterior pituitary hormone deficiency
   • Clinical features according to deficient hormonal axes
   • Dynamic testing and MRI
   • Safe sequence of hormonal replacement: glucocorticoid before levothyroxine
   • Sheehan syndrome after severe postpartum hemorrhage, including failure of lactation and postpartum amenorrhea

1. Acromegaly/gigantism
2. Hyperprolactinemia
3. Hypopituitarism/Sheehan syndrome

Acromegaly and Gigantism

1. Definition

One-line distinction:
GH excess before epiphyseal closure = gigantism.
GH excess after epiphyseal closure = acromegaly.

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A. Normal GH-IGF-1 Axis

Hypothalamus
   ↓ GHRH stimulates              ↓ Somatostatin inhibits
Anterior pituitary somatotroph
   ↓ GH
Liver and peripheral tissues
   ↓ IGF-1
Linear growth, bone/soft-tissue growth, anabolic effects

IGF-1 provides negative feedback:
↓ GH secretion and ↑ hypothalamic somatostatin

Important physiology

• GH secretion is pulsatile, highest during sleep.
• GH increases with exercise, fasting, stress, hypoglycemia, and puberty.
• GH is normally suppressed by hyperglycemia.
• Most growth-promoting effects of GH are mediated by IGF-1, mainly synthesized by the liver.
• Therefore, a random GH level is unreliable, whereas age-adjusted serum IGF-1 is the preferred screening test.

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B. Aetiology

1. Pituitary causes: most common

GH-secreting pituitary adenoma

• Usually a benign somatotroph adenoma
• Often a macroadenoma at diagnosis because manifestations develop slowly
• May co-secrete prolactin, as mammosomatotroph cells can produce both GH and prolactin

2. Genetic or familial causes

3. Rare non-pituitary causes

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C. Pathophysiology: Step-by-Step

GH-secreting pituitary adenoma
          ↓
Autonomous, persistent GH excess
          ↓
Increased hepatic and peripheral IGF-1 production
          ↓
1. Bone and cartilage growth
2. Soft-tissue proliferation
3. Insulin resistance
4. Organ enlargement
5. Tumor mass effects

1. Effects on skeleton and soft tissue

• Periosteal bone growth
• Enlargement of hands, feet, mandible, frontal bones
• Thickened skin and soft tissue
• Macroglossia and upper-airway tissue enlargement
• Visceral organ enlargement

2. Metabolic effects

• Decreases peripheral glucose uptake
• Increases lipolysis
• Increases hepatic glucose output
• Causes insulin resistance

3. Cardiovascular effects

• Hypertension
• Concentric ventricular hypertrophy
• Acromegalic cardiomyopathy
• Diastolic dysfunction, later systolic dysfunction
• Arrhythmias
• Heart failure

4. Tumor mass effects

Pituitary macroadenoma
       ↓
Optic chiasm compression → bitemporal hemianopia
Cavernous sinus invasion → diplopia, ophthalmoplegia
Normal pituitary compression → hypopituitarism
Raised intrasellar pressure → headache

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D. Clinical Features

1. General appearance

Acral and skeletal features

• Increase in shoe, glove, ring, and hat size
• Spade-like hands with thick, doughy soft tissue
• Broad fingers and toes
• Enlarged heel pad
• Frontal bossing
• Coarse facial features
• Enlarged nose, lips, and ears
• Prognathism: protruding lower jaw
• Widely spaced teeth
• Malocclusion
• Macroglossia
• Deep, rough, resonant voice

Gigantism

• Markedly increased height and long limbs
• Rapid growth velocity in a child or adolescent
• Delayed puberty may occur
• Features of acromegaly can coexist if disease persists after puberty

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2. Skin and soft tissue

• Thick, oily skin
• Hyperhidrosis
• Skin tags
• Excessive sweating with offensive body odor
• Deepened skin folds
• Enlarged tongue
• Soft-tissue swelling

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3. Musculoskeletal and neurological manifestations

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4. Cardiovascular manifestations

• Hypertension
• Left ventricular hypertrophy
• Cardiomyopathy
• Arrhythmias
• Ischemic heart disease
• Heart failure

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5. Respiratory manifestations

• Snoring
• Obstructive sleep apnea
• Daytime somnolence
• Difficult intubation due to macroglossia, soft-tissue upper airway enlargement, and altered facial anatomy

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6. Metabolic and endocrine manifestations

• Impaired glucose tolerance or diabetes mellitus
• Dyslipidemia
• Hyperphosphatemia due to increased renal phosphate reabsorption
• Hypercalciuria and renal stones
• Goiter or thyroid nodules
• Menstrual irregularity, infertility, decreased libido
• Erectile dysfunction
• Galactorrhea if prolactin is co-secreted
• Hypopituitarism from compression of normal pituitary tissue

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7. Gastrointestinal and neoplastic associations

• Colonic polyps
• Increased concern for colorectal neoplasia
• Increased thyroid nodules
• Consider colonoscopic screening, especially in patients with elevated IGF-1 or a history of colonic polyps.

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8. Features due to pituitary macroadenoma

• Headache
• Bitemporal hemianopia
• Reduced visual acuity
• Diplopia or ophthalmoplegia due to cavernous sinus involvement
• Hypopituitarism

Exam pearl: A patient with increased ring size, coarse facial features, excessive sweating, diabetes, headache, and bitemporal hemianopia has acromegaly due to a pituitary macroadenoma until proven otherwise.

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E. Investigations

Investigation strategy

Clinical suspicion
      ↓
Age-adjusted serum IGF-1
      ↓
If elevated or equivocal
      ↓
75-g oral glucose tolerance test with GH suppression test
      ↓
Failure of GH suppression confirms biochemical diagnosis
      ↓
Pituitary MRI with contrast
      ↓
Assess visual fields, pituitary function, and systemic complications

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1. Initial investigations

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2. Best screening test

Serum IGF-1

• Obtain an age-adjusted and sex-adjusted serum IGF-1.
• It reflects integrated GH secretion and is more stable than GH.
• A normal IGF-1 usually excludes acromegaly, provided there is no major confounder.

Conditions that can alter IGF-1 interpretation

• Pregnancy
• Puberty
• Liver disease
• Renal failure
• Malnutrition
• Uncontrolled diabetes mellitus
• Oral estrogen therapy

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3. Confirmatory test: 75-g oral glucose tolerance test

Principle

Procedure

1. Measure baseline GH.
2. Give 75 g oral glucose.
3. Measure GH serially over approximately 2 hours.

Interpretation

Do not diagnose acromegaly from a single random GH measurement.

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4. Localization: Pituitary MRI with gadolinium

Investigation of choice for localization

• Microadenoma or macroadenoma
• Suprasellar extension
• Optic chiasm compression
• Cavernous sinus invasion
• Surgical anatomy

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5. Visual assessment

• Macroadenoma is present
• Tumor abuts/compresses optic chiasm
• The patient has visual symptoms

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6. Full pituitary hormonal assessment

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F. Diagnosis

Diagnostic criteria

1. Typical clinical features, plus
2. Elevated age-adjusted IGF-1, plus
3. Failure of GH suppression on a 75-g oral glucose tolerance test, plus
4. Pituitary lesion on MRI in most patients.

Biochemical therapeutic targets

• Normal IGF-1 for age and sex
• Suppressed GH, often a nadir below 1 ng/mL during OGTT, with assay-specific targets

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G. Differential Diagnosis

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H. Management

Aims of treatment

1. Normalize GH and IGF-1.
2. Remove or reduce tumor mass.
3. Preserve normal pituitary function.
4. Improve or reverse complications.
5. Prevent recurrence and reduce mortality.

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Treatment algorithm

Confirmed acromegaly
       ↓
Pituitary MRI and assessment of surgical suitability
       ↓
Resectable pituitary adenoma
       ↓
Transsphenoidal surgery - first-line treatment
       ↓
Postoperative IGF-1/GH assessment
       ├─ Controlled → long-term surveillance
       └─ Persistent disease
             ↓
      Somatostatin receptor ligand ± cabergoline
             ↓
      Pegvisomant if IGF-1 remains uncontrolled
             ↓
      Radiotherapy for persistent/recurrent residual tumor

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1. Definitive first-line treatment: transsphenoidal surgery

Procedure

Indications

• Resectable pituitary adenoma
• Visual-field defect or optic chiasm compression
• Neurological compromise
• Large tumor causing mass effects
• Patient preference where surgical cure is likely

Advantages

• Rapid fall in GH levels
• Immediate decompression of optic pathways
• Tissue diagnosis
• May cure microadenomas and selected macroadenomas

Limitations

• Lower cure rate for invasive macroadenomas
• Risk of postoperative hypopituitarism
• CSF leak, diabetes insipidus, bleeding, and recurrence are possible

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2. Medical treatment

• For persistent disease after surgery
• When surgery is contraindicated or declined
• As primary treatment in selected invasive tumors
• Before surgery in selected patients to improve comorbidities or reduce tumor volume
• While awaiting radiotherapy effect

A. Somatostatin receptor ligands

Adverse effects

• Abdominal pain
• Nausea, diarrhea, steatorrhea
• Gallstones
• Glucose intolerance
• Bradycardia
• Injection-site reactions

B. Dopamine agonist

• Oral dopamine agonist
• Useful in mild biochemical disease
• Particularly useful if tumor co-secretes prolactin
• Can be used alone or combined with a somatostatin analogue

• Nausea
• Postural hypotension
• Headache
• Rare psychiatric/impulse-control effects
• Valvular monitoring may be considered with prolonged high-dose exposure

C. GH receptor antagonist

• Blocks peripheral GH receptor action
• Lowers IGF-1 effectively
• Does not directly shrink the pituitary tumor
• Monitor liver function and tumor size by MRI

• Elevated liver enzymes
• Injection-site reactions
• Possible tumor growth if GH secretion is not controlled, hence MRI surveillance

Viva pearl:
Somatostatin analogues reduce GH secretion.
Pegvisomant blocks GH action at its receptor and normalizes IGF-1, but may not shrink the adenoma.

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3. Radiotherapy

Indications

• Persistent or recurrent disease despite surgery and medication
• Residual tumor not surgically removable
• Progressive tumor growth

Types

• Conventional fractionated radiotherapy
• Stereotactic radiosurgery, such as Gamma Knife, for selected localized residual tumors

Limitations

• Effect is delayed, often years
• Medical therapy is continued until hormonal control is achieved
• Risk of hypopituitarism is significant
• Rare risks include optic injury, cerebrovascular disease, and secondary tumors

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4. Treatment of associated complications

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I. Follow-Up After Treatment

• Symptoms and physical features
• Serum IGF-1
• GH level, often including post-OGTT suppression assessment
• Pituitary MRI for residual/recurrent tumor
• Visual fields when relevant
• Other pituitary hormone deficiencies
• Glucose, blood pressure, cardiac status, sleep apnea, and colon health

Important postoperative point

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J. Complications of Acromegaly

1. Local tumor complications

• Headache
• Bitemporal hemianopia
• Ophthalmoplegia
• Hypopituitarism
• Pituitary apoplexy, rarely

2. Metabolic complications

• Insulin resistance
• Impaired glucose tolerance
• Diabetes mellitus
• Dyslipidemia
• Hyperphosphatemia
• Hypercalciuria and renal stones

3. Cardiovascular complications

• Hypertension
• Left ventricular hypertrophy
• Cardiomyopathy
• Arrhythmias
• Ischemic heart disease
• Heart failure

4. Respiratory complications

• Obstructive sleep apnea
• Difficult airway and difficult intubation
• Restrictive or obstructive ventilatory abnormalities

5. Musculoskeletal complications

• Osteoarthritis
• Arthropathy
• Carpal tunnel syndrome
• Spinal deformity
• Vertebral fractures may occur

6. Neoplastic associations

• Colonic polyps
• Colorectal malignancy concern
• Thyroid nodules

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K. Prognosis

• Untreated disease is associated with excess morbidity and premature mortality.
• Cardiovascular disease, diabetes, sleep apnea, and malignancy risk contribute to adverse outcomes.
• Prognosis improves markedly when IGF-1 normalizes and GH is adequately suppressed.
• Long-term surveillance is mandatory because residual or recurrent disease can occur.

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L. Acromegaly vs Gigantism

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M. Frequently Asked Viva Questions

1. What is the best screening test for acromegaly?

2. Why is random GH not useful?

3. What is the confirmatory test?

4. What is the commonest cause?

5. Why does acromegaly not increase height?

6. Why does gigantism occur in childhood?

7. What is the first-line treatment for a resectable pituitary adenoma?

8. Name three medical treatments.

• Octreotide or lanreotide
• Cabergoline
• Pegvisomant

9. What is the common visual-field defect?

10. Which hormone may be co-secreted?

11. What are the major causes of death in untreated acromegaly?

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N. High-Yield MCQs

MCQ 1

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MCQ 2

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MCQ 3

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MCQ 4

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MCQ 5

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O. Memory Aids

Clinical features: “BIG HANDS”

• B: Bitemporal hemianopia, blood pressure elevation
• I: Insulin resistance, increased IGF-1
• G: Gigantism if childhood onset
• H: Headache, hyperhidrosis, heart disease
• A: Acral enlargement, arthropathy, apnea
• N: Neuropathy, especially carpal tunnel
• D: Diabetes, dental spacing
• S: Skin tags, soft-tissue swelling, sleep apnea

Treatment: “SOM-CaP-R”

• SOM: Somatostatin analogues: octreotide, lanreotide, pasireotide
• Ca: Cabergoline
• P: Pegvisomant
• R: Radiotherapy
• Plus surgery as the usual first-line definitive therapy

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P. Five-Line Exam Summary

1. Acromegaly is GH excess after epiphyseal fusion, usually due to a pituitary somatotroph adenoma.
2. Gigantism is GH excess before epiphyseal closure, causing excessive linear growth.
3. Screen with age-adjusted IGF-1 and confirm by failure of GH suppression after a 75-g OGTT.
4. Localize with contrast MRI pituitary and assess visual fields plus other pituitary axes.
5. Transsphenoidal surgery is first-line for resectable tumors; residual disease is treated with somatostatin analogues, cabergoline, pegvisomant, and/or radiotherapy.