Evidence Grade B — Strong clinical evidence. 121 published studies, 102 human. 15 registered clinical trials.
Medically reviewed by a licensed medical professional
Protirelin (previously sold as Thypinone and Relefact TRH) is synthetic TRH — the brain hormone that controls thyroid function. It was used as a diagnostic injection to test pituitary function but has been discontinued from the US market after advances in blood test sensitivity made the provocative test unnecessary. It is notable as one of the smallest biologically active hormones known (just three amino acids), and its discovery contributed to a Nobel Prize in 1977.
Protirelin is also known by these brand and alternate names:
121 published studies: 102 human, 13 animal, 4 in-vitro, 6 reviews
Protirelin was previously marketed as Thypinone (Abbott) and Relefact TRH (Hoechst). The TRH stimulation test was a standard endocrine diagnostic procedure from the 1970s through the 1990s. It was discontinued from the US market in the early 2000s after advances in laboratory TSH measurement eliminated the need for a provocative test in most clinical scenarios.
Protirelin is notable as the smallest known biologically active peptide hormone (just three amino acids) and its discovery contributed to a Nobel Prize in Physiology or Medicine in 1977.
When injected intravenously, protirelin stimulates the pituitary to release TSH. In a healthy person, TSH rises predictably within 20–30 minutes. The pattern of response — whether exaggerated, normal, or absent — helped clinicians distinguish between different types of thyroid and pituitary disorders. This diagnostic utility was replaced by third-generation TSH assays that can detect extremely low TSH levels directly from a blood sample.
Research suggests protirelin's diagnostic utility was well established from the 1970s through the 1990s but was made obsolete by third-generation TSH assays that can detect extremely low TSH levels directly from a blood sample, eliminating the need for an injection-based test. Rare but serious adverse events included pituitary apoplexy in patients with undiagnosed large pituitary tumours. A related compound (taltirelin, an oral TRH analogue) is approved in Japan for a neurological condition, and TRH-based approaches are being explored for traumatic brain injury. No active development exists for protirelin itself in major markets.
PeptideTrace tracks 15 registered clinical trials for Protirelin sourced from ClinicalTrials.gov.
A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
Health Canada Market Authorisation
Protirelin (TRH) is a synthetic tripeptide (pyroGlu-His-Pro-NH2), MW 362.38 Da. Smallest known biologically active peptide hormone. N-terminal pyroglutamic acid and C-terminal prolinamide protect against exopeptidases. Identical to hypothalamic TRH. Previously marketed as Thypinone/Relefact TRH for diagnostic thyroid testing. Withdrawn from most markets as ultrasensitive TSH assays superseded it. Half-life ~5 minutes IV.
Research suggests binding to TRHR1 (Gq/11-coupled GPCR) on pituitary thyrotrophs and lactotrophs. Stimulates PLC/IP3/Ca2+/PKC, causing rapid TSH and prolactin release. TSH peaks 20-30 minutes post-IV. Exaggerated response = primary hypothyroidism; blunted = secondary hypothyroidism/hyperthyroidism; delayed = tertiary hypothyroidism.
Previously marketed as Thypinone (Abbott), Relefact TRH (Hoechst). TRH stimulation test was standard 1970s-1990s: 200-500 mcg IV, TSH at 0/15/30/60 min. Normal peak 5-25 mU/L above baseline. Replaced by third-generation TSH assays (sensitivity <0.01 mU/L). Discontinued from US market early 2000s.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism. In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.
Evidence Reviews
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This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
