Chapter 15 Quiz: Growth Hormone Secretagogues

22 items. Multiple choice and short answer. Answer key follows — work the whole quiz before opening it.

1. In the GH axis, which hormone acts as the brake on pituitary growth hormone release?

  • A. GHRH
  • B. IGF-1
  • C. Somatostatin
  • D. Ghrelin

2. Why is a single random blood measurement of growth hormone nearly uninterpretable?

  • A. Growth hormone degrades in the sample tube
  • B. Growth hormone is secreted in pulses and is near-undetectable between them
  • C. Assays for growth hormone are not standardized
  • D. Growth hormone circulates bound to albumin

3. Which molecule is the stable downstream measure used in place of growth hormone?

  • A. Ghrelin
  • B. Somatostatin
  • C. IGF-1
  • D. GHRH(1-29)

4. Sermorelin, CJC-1295, and tesamorelin all act at which receptor?

  • A. The ghrelin receptor (GHS-R)
  • B. The GHRH receptor
  • C. The growth hormone receptor
  • D. The IGF-1 receptor

5. Which of the following is not a peptide?

  • A. Ipamorelin
  • B. Tesamorelin
  • C. GHRP-6
  • D. MK-677

6. What does the DAC modification on CJC-1295 do?

  • A. Protects the molecule from stomach acid so it can be swallowed
  • B. Binds covalently to albumin, extending duration of action from minutes to days
  • C. Increases binding affinity at the GHRH receptor
  • D. Converts the molecule into a ghrelin receptor agonist

7. Ipamorelin was designed for selectivity. Which three activities was that selectivity intended to minimize? (short answer)

8. Tesamorelin is approved for which indication?

  • A. Age-related decline in growth hormone in healthy adults
  • B. Adult growth hormone deficiency
  • C. Reduction of excess visceral abdominal fat in HIV-associated lipodystrophy
  • D. Sarcopenia in older adults

9. In the two-year randomized trial of MK-677 in healthy older adults described in the chapter, which result was reported?

  • A. GH and IGF-1 rose, fat-free mass increased, and strength and function improved
  • B. GH and IGF-1 rose, fat-free mass increased, and strength and function did not improve
  • C. GH and IGF-1 did not rise meaningfully
  • D. The trial was stopped early for harm

10. What metabolic signal is documented for MK-677?

  • A. Reduced fasting glucose and improved insulin sensitivity
  • B. Increased blood glucose and reduced insulin sensitivity
  • C. No effect on glucose metabolism
  • D. Increased HDL cholesterol only

11. Which statement best captures the double lesson of tesamorelin?

  • A. The mechanism is unproven, so broad claims are unsupported
  • B. The mechanism is real, which supports broad claims for the class
  • C. Its existence proves the mechanism is real; its narrowness proves a real mechanism does not license broad claims
  • D. Its approval was a regulatory error later corrected

12. In the GH axis, elevated IGF-1 does what? (short answer, one sentence)

13. "Preserving the feedback loop" is often offered as a safety feature of secretagogues. What is the chapter's central objection to that framing? (short answer)

14. The GnRH precedent from Chapter 3 §3.5 establishes which of the following?

  • A. That extended-duration GHRH analogs suppress the GH axis
  • B. That continuous stimulation of a pulsatile axis can produce the opposite of the intended effect
  • C. That all peptide hormones must be given in pulses
  • D. That GnRH and GHRH act at the same receptor

15. Which of the following is a surrogate endpoint for this class?

  • A. Grip strength at 12 months
  • B. Serum IGF-1
  • C. Time to return to sport after injury
  • D. Fracture incidence

16. In the seven-step diagram, which step is the last one with established human evidence for CJC-1295 and ipamorelin? (short answer)

17. Give two distinct explanations for an increase in measured fat-free mass following GH axis stimulation. (short answer)

18. A compound known only by a laboratory code decades after its discovery tells you, with confidence, something about —

  • A. Its pharmacology
  • B. Its safety
  • C. Its regulatory history
  • D. Its potency

19. Write the chapter's rating for CJC-1295 combined with ipamorelin, including the claim it attaches to. (short answer)

20. Which rating rule prevents MK-677 from being downgraded because of the market it is sold in? (short answer)

21. A clinic advertises "restoration of youthful growth hormone levels, verified by lab testing." In two sentences, concede what is true and identify what is missing. (short answer)

22. Roughly what proportion of compounds entering human trials never reach approval, per Chapter 2 §2.9?

  • A. One in ten
  • B. Three in ten
  • C. Five in ten
  • D. Nine in ten
Answer key **1. C — Somatostatin.** GHRH is the accelerator; somatostatin is the brake. GH output at any moment is the net of the two. **2. B — Growth hormone is secreted in pulses and is near-undetectable between them.** A low value may mean a suppressed axis or simply a draw taken between bursts; a high value may mean a stimulated axis or a draw taken during one. **3. C — IGF-1.** Produced mainly by the liver in response to GH, it does not pulse, so it integrates GH exposure over a longer window. **4. B — The GHRH receptor.** GHRP-2, GHRP-6, ipamorelin, and MK-677 use the other door, the ghrelin receptor. **5. D — MK-677.** It is an orally active, long-acting, non-peptide ghrelin receptor agonist. Because it is not made of peptide bonds, digestive proteases have nothing to cut, which is why it can be swallowed. **6. B — Binds covalently to albumin, extending duration of action from minutes to days.** Albumin circulates for weeks; a peptide tethered to it is effectively hidden from kidney filtration and many proteases. **7.** Appetite stimulation, cortisol release, and prolactin release — the activities associated with GHRP-6 that ipamorelin's design aimed to avoid. Credit also for noting that selectivity is a statement about receptors, not a safety claim. **8. C — Reduction of excess visceral abdominal fat in HIV-associated lipodystrophy.** Note how many qualifiers that indication contains; each was earned by a trial and each limits what can honestly be claimed. **9. B — GH and IGF-1 rose, fat-free mass increased, and strength and function did not improve.** The surrogate performed flawlessly and the functional outcome did not follow. This is §15.7 in miniature. **10. B — Increased blood glucose and reduced insulin sensitivity.** This is measured, not inferred, and it is exactly what the physiology predicts: growth hormone is counter-regulatory and opposes insulin's action. **11. C.** Both halves are true simultaneously, and the chapter insists on holding them together. Any account of this class that drops either half is misleading. **12.** Elevated IGF-1 inhibits GH release and raises somatostatin — that is, the axis pushes back against any successful elevation. Credit for noting that the loop *opposes* you rather than protecting you. **13.** The loop is not on your side. A negative feedback loop exists to return the system to its set point and therefore actively resists the change you are trying to produce. It constrains the extreme, which has some value, but it erodes the intended effect by the same mechanism — so "preserves the feedback loop" is not a safety feature by itself. **14. B — That continuous stimulation of a pulsatile axis can produce the opposite of the intended effect.** Answer A is the trap: the same reversal has *not* been demonstrated for the GH axis, and asserting it would be exactly the mechanism-based overreach this book objects to. The GnRH case makes "sustained stimulation is at least as good as pulses" a claim requiring evidence — nothing more. **15. B — Serum IGF-1.** The others are outcomes people actually care about. **16.** Intermediate step 1 — GH and IGF-1 elevation. Human data supports that. Everything after it is mechanism, inference, and anecdote. (Accept "Step 3" from the seven-step diagram.) **17.** (i) An increase in contractile muscle tissue. (ii) Sodium and water retention, which body composition scans register as fat-free mass. Only the first would satisfy someone hoping to be stronger, and this is precisely why functional endpoints exist. **18. C — Its regulatory history.** Strong evidence there, and no evidence at all about pharmacology. The molecule may do exactly what its designers intended; nobody finished finding out. **19.** "CJC-1295 combined with ipamorelin improves body composition, recovery, or function in healthy adults: ⚠️→❌." The surrogate claim is supported; the outcome claim is not. Full credit requires naming the population (healthy adults) and the endpoint. **20.** Rule 4 — never downgrade with distaste. A two-year randomized controlled trial outweighs the company a compound keeps. **21.** Concede: these compounds do raise growth hormone and IGF-1, and a lab report showing that is real, not fabricated. Identify: a laboratory value is a surrogate, and no trial has shown that raising it produces the strength, recovery, or function being sold — the two-year trial that looked found the surrogate moved and the function did not. **22. D — Nine in ten.** Tesamorelin is the one in ten, and being the one in ten bought it a specific claim in a specific population and nothing more.