Acromegaly / GH excess
Pituitary somatotroph adenoma producing pathologic GH/IGF-1 excess — adult acromegaly 95%+ adenoma cases (gigantism = pediatric/adolescent equivalent before epiphyseal closure); rare GH-RH-producing tumors (pancreatic, lung). Features (insidious years): acral overgrowth + jaw prognathism + macroglossia + skin thickening + carpal tunnel + insulin resistance/T2D + hypertension + CARDIOMYOPATHY (major mortality driver) + arrhythmias + OSA + arthropathy + osteoporosis + hypogonadism + cancer surveillance (colorectal + thyroid + breast). Diagnostics: IGF-1 elevated + OGTT-suppressed GH + MRI pituitary + visual field testing. Standard of care: TRANSSPHENOIDAL SURGERY first-line; SSAs (octreotide LAR + lanreotide + pasireotide + oral octreotide Mycapssa FDA Jun 2020); GH receptor antagonist PEGVISOMANT (Somavert FDA 2003); dopamine agonists; stereotactic radiosurgery. EMERGING: PALTUSOTINE (CRN00808) oral non-peptide SSA Phase 3 PATHFNDR-1/2 positive 2023/2024 FDA submission pending. AACE 2024 + Endocrine Society + Acromegaly Community + AANS. **CRITICAL**: GH-stimulating peptides (sermorelin, CJC-1295, ipamorelin, MK-677, tesamorelin) ACTIVELY CONTRAINDICATED in active acromegaly; 2-5 year post-cure caution; tesamorelin FDA label contraindicates pituitary tumor history. Forty-ninth deliberate non-elevation.
What changes during this transition
Acromegaly is the editorially sharpest contraindication context in the entire library. Adult acromegaly is caused by a GH-secreting pituitary adenoma in 95%+ of cases (rare GHRH-producing pancreatic/lung tumors and ectopic GH account for the rest); pediatric/adolescent equivalent before epiphyseal closure is gigantism. IGF-1 mediates most downstream clinical features — acral overgrowth, jaw prognathism, macroglossia, skin thickening, carpal tunnel, insulin resistance progressing to T2D, hypertension, dyslipidemia, OSA, arthropathy, spinal stenosis, hypogonadism, and elevated colorectal/thyroid/breast cancer surveillance burden. Cardiomyopathy with heart failure, arrhythmias, and valvular involvement is the single largest mortality driver if disease activity is uncontrolled. Diagnostics anchor on IGF-1 elevation and failure to suppress GH below 1 ng/mL on a 75g OGTT, paired with pituitary MRI and visual field testing for chiasmal compression. Standard of care follows AACE 2024 and Endocrine Society guidance: transsphenoidal surgery is first-line for resectable adenomas; medical therapy uses somatostatin analogs (octreotide LAR / Sandostatin, lanreotide / Somatuline Depot, pasireotide / Signifor, and oral octreotide / Mycapssa — FDA-approved June 2020 as the first oral SSA), the GH receptor antagonist pegvisomant (Somavert, FDA 2003) which blocks GH receptor binding and normalizes IGF-1 without shrinking tumor, and dopamine agonists (cabergoline, bromocriptine) for partial efficacy in selected cases. Stereotactic radiosurgery (Gamma Knife) addresses residual disease. Paltusotine (CRN00808), an oral non-peptide SSA, posted positive Phase 3 PATHFNDR-1 and PATHFNDR-2 data in 2023-2024 with FDA submission pending — the first credible oral alternative to injectable SSAs at full efficacy. Treatment goals are normalized IGF-1, controlled GH, tumor reduction, pituitary preservation, and aggressive cardiovascular risk management. The reason acromegaly belongs in the Juno library is not because there is a peptide protocol for it — there isn't, and there shouldn't be. It's because the entire body-building / longevity / 'peptide stack' culture aggressively markets growth-hormone-stimulating compounds (sermorelin, CJC-1295 with or without DAC, ipamorelin, hexarelin, tesamorelin, MK-677 / ibutamoren) as wellness interventions. Every one of these is a sharp contraindication in active acromegaly because they push the same axis the disease is already pathologically over-driving. Patients who are diagnosed mid-protocol, partners or family members researching after a diagnosis, post-surgical patients in biochemical remission considering whether 'low-dose GH peptides' are safe, and clinicians fielding patient questions all need a clear, unflinching reference. Juno's job in this context is to be the source that says no — explicitly, with mechanism — and then redirects to endocrinology. Resources: Acromegaly Community (acromegalycommunity.org), AANS for surgical perspective, AACE 2024 Clinical Practice Guideline, Endocrine Society.
Important caveat
Active or biochemically uncontrolled acromegaly is a HARD REFUSAL for every GH-axis peptide in this library — sermorelin, CJC-1295 (with or without DAC), tesamorelin, ipamorelin, hexarelin, and MK-677 / ibutamoren all stimulate the exact axis the disease over-drives. Tesamorelin specifically has an FDA label contraindication for pituitary tumor history, pituitary surgery, head trauma, or active malignancy. Even in surgically cured patients with normalized IGF-1, the standard endocrine caution is a minimum 2-5 year period of demonstrated biochemical control with periodic surveillance before any GH-stimulating intervention should even be a conversation, and that conversation belongs with the patient's endocrinologist, not a peptide clinician. Juno does not provide a 'safe' peptide protocol for acromegaly under any framing. **MEDICATION RECONCILIATION**: MK-677 / ibutamoren / Nutrobal is commonly missed because it's sold as a supplement — ask explicitly. **WORKUP PRECEDENCE**: if acromegaly is suspected (acral changes, jaw prognathism, ring/shoe size progression, new T2D + hypertension + OSA cluster, macroglossia), STOP any GH-axis peptide protocol before IGF-1 / OGTT-GH testing — interpretation depends on it. **EMERGENCY-LIKE NUANCE**: visual changes (chiasmal compression), severe headache (pituitary apoplexy), heart failure symptoms warrant urgent evaluation. CARDIOMYOPATHY surveillance non-negotiable. CANCER SURVEILLANCE: colorectal + thyroid + breast per AACE 2024. Pregnancy in acromegaly is high-risk; coordinate endocrinology + maternal-fetal medicine; SSA generally continued; pegvisomant pregnancy data limited. WADA athletes: GH-axis peptides (CJC-1295, tesamorelin, ipamorelin, MK-677) prohibited at all times. AACE 2024 + Endocrine Society + Acromegaly Community + AANS.
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