Chapter 32 · Module 3 Visual Summary
Growth Hormone Axis Pharmacology
Somatostatin analogs, GH replacement, secretagogues, and pegvisomant
SSA = somatostatin receptor analog  ·  IGF-1 = insulin-like growth factor-1  ·  GH = growth hormone  ·  SSTR = somatostatin receptor subtype  ·  GHRH = growth hormone-releasing hormone  ·  GHSR = growth hormone secretagogue receptor  ·  DPP-4 = dipeptidyl peptidase-4  ·  GLP-1 = glucagon-like peptide-1  ·  HPA = hypothalamic-pituitary-adrenal axis
GH Axis Drug Classes at a Glance
Drug Class Prototype(s) Mechanism Primary Use Monitor
SSTR2/5 selective SSA Octreotide LAR, Lanreotide Autogel Gi-coupled SSTR2/5 activation ↓ GH, ↓ IGF-1 Acromegaly (first-line after surgery); carcinoid, VIPoma GH + IGF-1; glucose; gallstones
Pan-SSTR agonist Pasireotide LAR SSTR1/2/3/5 activation; SSTR5 affinity 40x octreotide SSA-resistant acromegaly; Cushing disease GH + IGF-1; glucose closely (57–73% hyperglycemia); HbA1c
GHRH analog Tesamorelin GHRH-R Gs activation → endogenous GH release HIV-associated lipodystrophy (visceral fat reduction) IGF-1; glucose; contraindicated in active malignancy
GHSR agonist (oral) Macimorelin Ghrelin receptor (GHSR-1a) activation → GH pulse Diagnosis of adult GH deficiency (single-dose test) Peak GH at 30/45/60/90 min; baseline ECG; avoid CYP3A4 inducers
GH replacement Somatropin Recombinant GH → IGF-1 production Adult GH deficiency; pediatric growth failure IGF-1; fasting glucose; HbA1c; DEXA; assess adrenal status before starting
GH receptor antagonist Pegvisomant Blocks GH receptor dimerization → ↓ IGF-1 Acromegaly (especially SSA-resistant) IGF-1 ONLY (not GH); LFTs q6 months; MRI annually
Somatostatin Analogs — Formulation and Key Differences
Octreotide LAR
PLGA Microsphere IM Depot
  • 20, 30, 40 mg IM every 28 days
  • Bridge with SC octreotide for ~14 days after first LAR injection
  • SSTR2/5-selective
  • GH normalization in ~50–60% of acromegaly patients
  • IGF-1 normalization in 30–50%
  • Hyperglycemia: 10–20%
  • Cholelithiasis: 20–30% long-term
Lanreotide Autogel
Deep SC Self-Assembling Gel
  • 60, 90, 120 mg SC every 4 weeks
  • No 14-day bridge needed — immediate therapeutic levels
  • Extended intervals (q6–8 weeks) for controlled patients
  • SSTR2/5-selective; comparable efficacy to octreotide LAR
  • Fecal elimination (<5% renal) — no renal dose adjustment
  • Hyperglycemia: 10–20%
Pasireotide LAR
Pan-SSTR Agonist — Second-Line
  • 40 or 60 mg IM every 28 days
  • SSTR1/2/3/5; SSTR5 affinity 40x octreotide
  • Biochemical control in 31–38% of SSA-resistant patients (PAOLA trial)
  • Cushing disease: corticotrophs express SSTR5 > SSTR2
  • Hyperglycemia 57–73% — prefer GLP-1 agonist or insulin
  • DPP-4 inhibitors and metformin largely ineffective
Pegvisomant vs. Somatostatin Analogs — Key Distinctions
Pegvisomant (Somavert)
GH Receptor Antagonist
  • PEGylated GH analog — blocks receptor dimerization
  • t½ ~6 days; once-daily or every-other-day SC
  • IGF-1 normalization in 90–97% of patients
  • GH secretion NOT suppressed — GH rises during therapy
  • Monitor IGF-1 ONLY — not GH
  • Does NOT reduce tumor volume — MRI annually
  • Hepatotoxicity: LFTs at baseline and every 6 months
  • Stop if ALT/AST >5x upper limit of normal
Somatropin Drug Interactions
CYP3A4 Induction Consequences
  • Induces CYP3A4 and CYP2C19
  • Accelerates glucocorticoid clearance → may unmask adrenal insufficiency in hypopituitary patients
  • Check HPA axis before starting; increase hydrocortisone dose 20–30% if needed
  • Reduces cyclosporine levels → monitor in transplant patients
  • Women on oral (not transdermal) estrogen require higher somatropin doses
  • Contraindicated in active malignancy and acute critical illness
Acromegaly Treatment Algorithm
Step 1: Transsphenoidal surgery (first-line all resectable tumors).  •  Step 2 (residual disease): Octreotide LAR or lanreotide Autogel — uptitrate over 6–12 months; target GH <1 ng/mL and IGF-1 normal.  •  Step 3 (inadequate SSA control): (a) Switch to pasireotide LAR if both GH and IGF-1 elevated and metabolic risk acceptable. (b) Add pegvisomant to SSA if IGF-1 alone elevated — best IGF-1 normalization rates. (c) Add cabergoline to SSA if prolactin co-elevated (D2R-expressing tumor).  •  Step 4 (pegvisomant monotherapy): monitor IGF-1 only, not GH; annual pituitary MRI.