Give a clinical case 10 marks on gigantism acromegaly and growth hormone , physiology , mbbs pre prof question
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Clinical Case: Gigantism, Acromegaly, and Growth Hormone - 10 Marks
CLINICAL CASE
Case Presentation:
A 35-year-old woman presents with a 7-year history of progressive enlargement of her hands and feet, prompting her to change her ring, shoe, and glove sizes twice. She also complains of persistent headaches, excessive sweating at rest, deepening of her voice, and two operations for bilateral carpal tunnel syndrome in the past 4 years. Her husband has noticed increasing coarsening of her facial features. On examination: prominent brow (frontal bossing), prognathism (protruding jaw), widely spaced teeth, macroglossia, large doughy hands, and bitemporal hemianopia on visual field testing. BP 150/95 mmHg. Random blood glucose 8.9 mmol/L.
"On the basis of the above history and examination, answer the following:"
PART A: PHYSIOLOGY OF GROWTH HORMONE (GH) [3 Marks]
Source and Structure
- GH (somatotropin) is a 191-amino acid single-chain polypeptide secreted by somatotroph cells of the anterior pituitary gland.
- Secretion is pulsatile, with the highest pulses occurring during deep (slow-wave) sleep and at puberty.
Regulation of GH Secretion
The hypothalamo-pituitary axis controls GH via a dual-control mechanism:
| Factor | Source | Effect on GH |
|---|---|---|
| GHRH (Growth Hormone-Releasing Hormone) | Hypothalamus | Stimulates GH synthesis & secretion via cAMP and IP3/Ca2+ |
| Somatostatin (SRIF) | Hypothalamus | Inhibits GH secretion by blocking GHRH action via Gi-adenylyl cyclase |
| Ghrelin | Stomach/GIT | Stimulates GH secretion via GHSR receptors |
| IGF-1 (Somatomedin-C) | Liver | Negative feedback - inhibits GH at both hypothalamus and pituitary |
Feedback loops (3 types):
- Ultrashort: GHRH inhibits its own secretion from hypothalamus
- Short: GH stimulates somatostatin secretion from hypothalamus
- Long: IGF-1 (produced in liver in response to GH) stimulates somatostatin and inhibits GHRH
Stimuli increasing GH: Hypoglycemia, fasting/starvation, exercise, stress, trauma, fever, sleep, puberty, estrogen
Stimuli decreasing GH: Hyperglycemia (oral glucose), somatostatin, obesity, old age
Actions of GH
1. Linear growth (pre-pubertal, main function):
- GH stimulates chondrocytes at epiphyseal plates - increased DNA, RNA, and protein synthesis in cartilage
- Widens epiphyseal plates; more bone laid down at ends of long bones
- Mediated largely via IGF-1 (somatomedin C) produced by liver
2. Metabolic effects (direct GH actions):
- Diabetogenic / Anti-insulin effect: GH causes insulin resistance - decreases glucose uptake in muscle and adipose tissue → raises blood glucose → raises blood insulin levels
- Lipolysis: Promotes fat breakdown in adipose tissue (fat-mobilizing effect)
- Protein anabolism: Increases amino acid uptake, stimulates DNA, RNA, and protein synthesis in virtually all organs → increased lean body mass and organ growth
(Costanzo Physiology, 7th Ed.)
PART B: WHAT IS THE MOST LIKELY DIAGNOSIS? DEFINE GIGANTISM vs ACROMEGALY [2 Marks]
Diagnosis in this case: ACROMEGALY (due to excess GH after epiphyseal fusion)
Gigantism vs. Acromegaly
| Feature | Gigantism | Acromegaly |
|---|---|---|
| Timing of GH excess | Before puberty (before epiphyseal plate closure) | After puberty (after epiphyseal plate closure) |
| Key feature | Excessive linear (height) growth - patients may exceed 7-8 feet | No increase in height; acral and soft tissue overgrowth |
| Epiphyseal plates | Open - respond to GH | Closed - cannot respond |
| Bone response | Longitudinal bone growth | Periosteal (width) overgrowth only |
| Common cause | GH-secreting pituitary adenoma in childhood | GH-secreting pituitary adenoma in adulthood |
"The presence of excessive amounts of circulating GH before closure of the epiphyses leads to gigantism. If the epiphyses have closed, the only tissue still capable of responding to GH will grow, leading to the clinical syndrome of acromegaly."
- Bradley & Daroff's Neurology in Clinical Practice
PART C: CLINICAL FEATURES OF ACROMEGALY [2 Marks]
GH-excess effects:
- Acral changes: Enlarged hands (doughy/spade-like), feet, jaw (prognathism), nose, supraorbital ridges (frontal bossing)
- Soft tissue: Macroglossia, skin tags, thickened skin
- Hyperhidrosis (excessive sweating at rest) - very common
- Voice change: Deepening due to laryngeal hypertrophy
Metabolic effects:
- Diabetes mellitus / impaired glucose tolerance (GH is diabetogenic)
- Hypertension → risk of myocardial hypertrophy, ischemic heart disease, heart failure
Mass effects of pituitary adenoma (macroadenoma in 75% at diagnosis):
- Headaches (up to 60% of patients)
- Bitemporal hemianopia (optic chiasm compression)
- Nerve entrapment: Carpal tunnel syndrome (bilateral) - a classic early clue often missed for years
Others:
- Sleep apnea (pharyngeal soft tissue overgrowth)
- Menstrual irregularities
- Arthralgia, proximal muscle weakness
- Increased risk of colonic polyps and colon cancer
Notably, carpal tunnel surgery done bilaterally 3-5 years before acromegaly diagnosis is a well-recognized pattern in the literature. (Goldman-Cecil Medicine, Bradley & Daroff's Neurology)
PART D: DIAGNOSIS [1.5 Marks]
Step 1 - Biochemical Confirmation:
- Serum IGF-1 (Somatomedin-C) - single best screening test; correlates with daily GH secretion and disease activity. Elevated in acromegaly.
- Oral Glucose Tolerance Test (OGTT) - Gold standard for confirmation:
- Normal: 75g glucose suppresses GH to <1 ng/mL (polyclonal assay) or <0.4 ng/mL (IRMA)
- Acromegaly: GH fails to suppress (paradoxically may even rise)
- Random GH alone is not reliable (pulsatile secretion)
- Also measure serum prolactin (many tumors co-secrete GH + prolactin)
Step 2 - Imaging:
- MRI pituitary - investigation of choice; shows macroadenoma in 90% of cases
- 75% are macroadenomas (>1 cm) at diagnosis due to typical 10-year diagnostic delay
PART E: TREATMENT [1.5 Marks]
Goal: Normalize GH and IGF-1 levels, reduce tumor mass, prevent recurrence, avoid hypopituitarism
| Modality | Details |
|---|---|
| Surgery (1st line) | Transsphenoidal resection - cures 80-90% of microadenomas; <30% cure for macroadenomas |
| Somatostatin analogues (medical) | Octreotide LAR, Lanreotide, Pasireotide LAR (IM every 4 weeks). Normalize IGF-1 in 50-60%. SE: diarrhea, cholelithiasis |
| Dopamine agonists | Cabergoline (0.5-1 mg twice/week) - normalizes GH/IGF-1 in ~30% alone; useful adjunct |
| GH receptor antagonist | Pegvisomant (daily SC injection) - blocks GH receptor; normalizes IGF-1 in >90% |
| Radiation | Stereotactic radiotherapy - adjunctive only; takes 5-10 years to lower GH; high risk of hypopituitarism |
SUMMARY TABLE (for quick revision)
| Feature | Acromegaly |
|---|---|
| Cause | GH-secreting pituitary adenoma (usually macroadenoma) |
| Age | 4th-5th decade |
| Key symptom | Enlarged hands/feet, coarse facies, headache, sweating |
| Key sign | Prognathism, bitemporal hemianopia, carpal tunnel |
| Best test | IGF-1 + OGTT (GH non-suppression) |
| Imaging | MRI pituitary |
| 1st line Rx | Transsphenoidal surgery |
| Medical Rx | Somatostatin analogues (octreotide) |
Sources: Goldman-Cecil Medicine (International Ed.), Costanzo Physiology 7th Ed., Bradley & Daroff's Neurology in Clinical Practice - all from the medical textbook library.
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