Chapter 14 Quiz

22 items. Multiple choice and short answer. Answer key at the bottom — write your answers before you open it.

Multiple choice

1. Human growth hormone is:

  • a) 51 amino acids in two disulfide-linked chains
  • b) 191 amino acids in a single chain, about 22 kDa
  • c) 70 amino acids, structurally similar to proinsulin
  • d) 30 amino acids, produced in the gut

2. The hypothalamic hormone that inhibits pituitary growth hormone release is:

  • a) GHRH
  • b) IGF-1
  • c) Somatostatin
  • d) Ghrelin

3. A single random blood measurement of growth hormone is nearly uninterpretable primarily because:

  • a) The assay is unreliable
  • b) Secretion is pulsatile, mostly nocturnal, and near-undetectable between bursts
  • c) Growth hormone is bound to carrier proteins that interfere with measurement
  • d) Levels vary with posture and hydration

4. IGF-1 is used as the standard screening measurement instead of growth hormone because:

  • a) It is cheaper to measure
  • b) It is produced only in the liver
  • c) It is largely protein-bound and therefore stable over days, acting as an integrator of recent growth hormone exposure
  • d) It is unaffected by nutrition, liver function, or age

5. Which of the following is a direct action of growth hormone rather than an IGF-1-mediated one?

  • a) Longitudinal bone growth at the growth plate
  • b) Inhibition of apoptosis in dividing cells
  • c) Lipolysis in adipose tissue
  • d) Muscle protein synthesis

6. Growth hormone is described as counter-regulatory, which means it:

  • a) Opposes insulin and raises blood glucose
  • b) Is regulated by a counter-current mechanism in the pituitary
  • c) Lowers blood glucose in the same way insulin does
  • d) Counteracts cortisol

7. In the 1990 Rudman study, the comparison group:

  • a) Received placebo injections and was blinded
  • b) Received a lower dose of growth hormone
  • c) Received no treatment
  • d) Was drawn from a separate published cohort

8. The single most important limitation of the Rudman study, for evaluating anti-aging claims, is that:

  • a) It was published in 1990 and is therefore outdated
  • b) Its endpoints were body composition — surrogates — and it did not measure strength, function, or long-term safety
  • c) The participants were all men
  • d) It has never been replicated

9. Somatopause refers to:

  • a) The abrupt cessation of growth hormone production in late middle age
  • b) The gradual age-related decline in growth hormone secretion and IGF-1, roughly 14% per decade after about age 30
  • c) The suppression of endogenous growth hormone by exogenous administration
  • d) The period between nocturnal secretory pulses

10. Which statement about the somatopause debate is accurate as of this writing?

  • a) It has been established that the decline is pathological and should be treated
  • b) It has been established that the decline is protective and should never be treated
  • c) Whether the decline is pathology or normal physiology is genuinely contested
  • d) The decline has not been reliably demonstrated

11. Acromegaly is:

  • a) Growth hormone deficiency in adulthood
  • b) Chronic growth hormone excess in adulthood, usually from a pituitary adenoma
  • c) Growth hormone excess beginning before growth plate closure
  • d) Insensitivity to growth hormone at the receptor

12. The feature of the acromegaly literature that most strengthens the causal interpretation is:

  • a) The large number of published case reports
  • b) That excess mortality is substantially reduced when the hormone excess is brought under biochemical control
  • c) That the condition is rare
  • d) That patients often have a visible physical phenotype

13. Before recombinant production, human growth hormone was obtained from cadaver pituitaries. Some preparations transmitted:

  • a) Hepatitis C
  • b) HIV
  • c) Creutzfeldt-Jakob disease, via prions
  • d) Tuberculosis

14. Which of these is the most accurate statement of the IGF-1 and cancer evidence?

  • a) Growth hormone has been shown to cause cancer in humans
  • b) There is no evidence of any relationship between IGF-1 and cancer
  • c) Higher IGF-1 has been observationally associated with several cancers; confounding is substantial and no causal claim is established
  • d) IGF-1 protects against cancer by promoting apoptosis

15. Under Chapter 5's framework, growth hormone given to a healthy 60-year-old with normal pituitary function is best described as:

  • a) Replacement of an absent signal, predicting durable benefit
  • b) An override of an intact system, predicting adaptation
  • c) A surrogate intervention
  • d) A frontier application

Rating skill

16. A claim is presented as: "Growth hormone: ⚠️ Promising but preliminary." What is the single most important thing wrong with the way this rating has been written?

  • a) ⚠️ is the wrong tier
  • b) It is not date-stamped
  • c) It attaches a rating to a molecule rather than to a claim with a population and an endpoint
  • d) It does not name what would change it

17. Someone argues: "Growth hormone drives IGF-1, IGF-1 is anabolic and anti-apoptotic, so the anti-aging claim should be rated at least ⚠️." Which frozen rule does this violate?

  • a) A rating attaches to a claim, not a molecule
  • b) Never upgrade a rating with mechanism
  • c) Never downgrade a rating with distaste
  • d) Every rating must be falsifiable

18. Someone argues: "Growth hormone is a bodybuilding drug pushed by shady longevity clinics, so obviously the evidence is junk." Which frozen rule does this violate, and does it change the rating in this chapter?

  • a) Never downgrade with distaste; and no, the ❌ rests on endpoint selection and trial results
  • b) Never upgrade with mechanism; and yes, the rating should be lower
  • c) One molecule, many ratings; and yes, the rating should be split further
  • d) A rating attaches to a claim; and no, the rating is unaffected

19. Which of the following would most directly move the anti-aging claim off ❌?

  • a) A larger trial confirming that lean mass increases and fat mass decreases
  • b) A new mechanistic study showing growth hormone activates additional repair pathways
  • c) A multi-year randomized, blinded, placebo-controlled trial in healthy older adults with prespecified functional and clinical endpoints showing benefit that outweighs harms
  • d) A large survey of clinic patients reporting improved well-being

Short answer

20. In no more than three sentences, state what the Rudman study established and what it could not establish. Your answer must include the sentence this book requires to accompany every mention of it.

21. A patient asks: "My growth hormone level came back undetectable. Do I have a deficiency?" Answer in three or four sentences, explaining what the result does and does not tell you and what would be done next.

22. Explain, in four sentences or fewer, why this chapter issues a ✅ and a ❌ for the same molecule, and why that is not a contradiction. Name the frozen rule that makes it coherent.

Answer key **1. b.** 191 amino acids, single chain, approximately 22 kDa, from the anterior pituitary. (a) is insulin, (c) is IGF-1, (d) describes GLP-1. **2. c.** Somatostatin — the brake. GHRH is the accelerator; IGF-1 provides feedback inhibition but is not hypothalamic; ghrelin stimulates rather than inhibits. **3. b.** Pulsatility is the reason. Between bursts, circulating growth hormone falls to near-zero, so a healthy person sampled at the wrong moment reads as undetectable. **4. c.** IGF-1 is largely bound to carrier proteins (principally IGFBP-3), which greatly extends its circulating lifetime and makes it a running average of recent growth hormone exposure. (d) is false — IGF-1 is influenced by nutrition, liver function, thyroid status, illness, and age, which is exactly why a low IGF-1 is a reason to investigate rather than a diagnosis. **5. c.** Lipolysis is a direct growth hormone action. Longitudinal bone growth, apoptosis inhibition, and muscle protein synthesis are principally IGF-1-mediated. **6. a.** Counter-regulatory means it opposes insulin's peripheral action and promotes hepatic glucose output — it raises blood glucose. This single fact drives much of §14.7's risk profile and essentially all of acromegaly's metabolic disease. **7. c.** The controls received no treatment, not placebo. This is why the study is not blinded in the modern sense. **8. b.** The endpoints were surrogates. Small size, 1990 publication date, and an all-male sample are all real limitations, but the decisive one is that it measured the proxy rather than any goal. Notably, (d) is simply false — the body composition finding has replicated repeatedly. **9. b.** Gradual decline, roughly 14% per decade after about 30, stated as approximate. (c) describes feedback suppression from exogenous administration, which is a different phenomenon. **10. c.** Genuinely contested. Reduced growth/IGF-1 signaling is associated with extended lifespan in model organisms, while adult growth hormone deficiency is a real syndrome with real morbidity. Both bodies of evidence are real and they point in different directions. **11. b.** Adult-onset growth hormone excess, usually a pituitary adenoma. (c) is gigantism; (d) is Laron syndrome. **12. b.** The improvement in mortality with biochemical control functions as a dose-response relationship, which is what elevates the evidence from "sick people have high hormone levels" to "the hormone level is doing the damage." **13. c.** Creutzfeldt-Jakob disease via prions, with incubation periods measured in decades. Distribution was halted in 1985. **14. c.** Association exists; confounding is substantial (IGF-1 tracks nutrition, body size, insulin, activity, socioeconomic position); reverse causation is live; causation is not established. Both (a) and (b) overstate — one in each direction. **15. b.** Override of an intact system. The prediction is adaptation: exogenous growth hormone raises IGF-1, which suppresses pituitary release and raises somatostatin, so endogenous production falls. That is expected physiology, not a malfunction. **16. c.** The rating is attached to a molecule. Rule 1 requires a claim with a population and an endpoint. Options (b) and (d) name real additional defects — every rating should be date-stamped and falsifiable — but the structural error is the missing claim, because without it the rating cannot be evaluated at all. Growth hormone has at least two correct ratings simultaneously. **17. b.** Never upgrade with mechanism. Every link in the mechanistic chain is real, and it is still not evidence. Roughly nine in ten compounds entering human trials with coherent mechanisms never reach approval. **18. a.** Never downgrade with distaste. Strip away every social association and the ❌ is unchanged, because it rests on endpoint selection and on what the trials measured and found. **19. c.** The falsification condition named in the rating itself. (a) reconfirms a surrogate; (b) is a mechanism upgrade; (d) is uncontrolled, unblinded, and self-selected. **20.** Model answer: *Twelve men over 60, six months of growth hormone versus untreated controls: increased lean mass and decreased fat mass. It did not measure strength, function, or long-term safety.* It therefore established that growth hormone changes body composition in older men over six months — a real, replicated finding — and could not establish anything about function, durability, or harm. **21.** Model answer: An undetectable random growth hormone level is expected in healthy people, because secretion is pulsatile and falls to near-zero between nocturnal bursts, so this result on its own tells you almost nothing. Diagnosis starts from a structural or historical reason to suspect pituitary failure, uses IGF-1 as a stable screening measurement — noting that a normal IGF-1 does not exclude adult deficiency — and generally proceeds to dynamic stimulation testing, which measures a response rather than a snapshot. The other pituitary axes would be assessed as well. Credit for recognizing that the question cannot be answered from the number presented. **22.** Model answer: The ✅ covers replacement in documented deficiency, where controlled trials show durable benefit on endpoints including growth itself; the ❌ covers anti-aging and functional claims in healthy adults, where the demonstrated effect is on a surrogate, function did not follow, and long-term safety is unestablished. These are different populations and different endpoints, so they are two facts rather than a contradiction. The frozen rule is **one molecule, many ratings** — and its corollary, that a rating attaches to a claim, not to a molecule. Full credit requires noting that the ❌ describes the evidence for a claim, not a statement that growth hormone does nothing.