Rovatirelin ameliorates motor dysfunction in the cytosine arabinoside-induced rat model of spinocerebellar degeneration via acetylcholine and dopamine neurotransmission.

Thyrotropin-releasing hormone (TRH) and the TRH mimetic taltirelin have been used in Japan for the treatment of spinocerebellar degeneration (SCD), a type of progressive ataxia. A TRH mimetic, rovatirelin, ameliorates ataxia symptoms in the rolling mouse Nagoya, a hereditary SCD model. The aim of this study was to verify the effects of oral administration of rovatirelin on a cytosine arabinoside (Ara-C)-induced ataxia rat model, a sporadic SCD model characterized by gait abnormalities and falls because of cerebellar atrophy and investigate the central nervous system mechanism associated with rovatirelin-mediated amelioration of motor dysfunction in these rats. Rovatirelin at ≥3 mg/kg significantly decreased the fall index, which is a primary endpoint of improved motor function calculated by dividing the number of falls by the locomotor activity, in both male and female rats with Ara-C-induced ataxia. Furthermore, rovatirelin caused a significant increase in locomotor activity in a dose-dependent manner. Taltirelin at ≥30 mg/kg ameliorated motor dysfunction in ataxic rats. Moreover, rovatirelin significantly increased acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and dopamine (DA) levels in the nucleus accumbens (NAc) at ≥3 mg/kg and significantly increased DA levels in the dorsal striatum at ≥10 mg/kg in normal rats. In conclusion, oral administration of rovatirelin ameliorates motor dysfunction in rats with Ara-C-induced ataxia, owing to its ACh-increasing effects in the mPFC and DA-increasing effects in the dorsal striatum and NAc. Furthermore, the effects of rovatirelin were more potent than those of taltirelin.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use. OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification. MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome. AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

Repurposing of FDA-Approved Drugs for Treating Iatrogenic Botulism: A Paired 3D-QSAR/Docking Approach†.

Botulinum neurotoxin (BoNT) is widely used for the treatment of spasticity, focal dystonia, chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, treatment with botulinum toxin is a safe procedure when conducted by clinicians with expertise, and local side effects are rare and transient. However, occasionally adverse effects can occur due to the spread of the drug to nontargeted muscles and organs, producing dry mouth, fatigue, and flu-like symptoms, up to signs of systemic botulism, which appears to be more frequent in children treated for spasticity than in adults. In silico 3D-QSAR and molecular docking studies were performed to build a structure-based model on selected potent known botulinum neurotoxin type A inhibitors; this was used to screen the US Food and Drug Administration (FDA) database. Thirty molecules were identified as possible light-chain BoNT/A inhibitors. In this study, we applied a well-established ligand- and structure-based methodology for the identification of hit compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by other compounds can be considered a starting point for investigations of selected compounds that could bypass much of the time and costs involved in the drug approval process.

Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease.

BACKGROUND: Thyrotropin-releasing hormones (TRH) added to prenatal corticosteroids has been suggested as a way to further reduce breathing problems and neonatal lung disease in infants born preterm. OBJECTIVES: To assess the effects of giving prenatal TRH in addition to corticosteroids to women at risk of preterm birth for the prevention of neonatal respiratory disease. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013) and reference lists of retrieved studies. We also contacted trial authors. SELECTION CRITERIA: Randomised controlled trials in women at sufficient risk of preterm birth to warrant the use of prenatal corticosteroids to promote lung maturity. TRH and corticosteroids were compared with corticosteroids, with or without placebo. DATA COLLECTION AND ANALYSIS: All assessments of trial eligibility, risk of bias and data extractions were independently carried out by at least two review authors. MAIN RESULTS: Over 4600 women were recruited into the 15 trials included in the review, however two trials did not contribute any outcome data to the review. The trials had a moderate risk of bias. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of death prior to hospital discharge (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.86 to 1.27, six trials, 3694 infants), neonatal respiratory distress syndrome (average RR 1.05, 95% CI 0.91 to 1.22, nine trials, 3833 infants), or chronic lung disease (RR 1.01, 95% CI 0.85 to 1.19, five trials, 2511 infants), and did not improve any of the secondary fetal, neonatal or childhood outcomes assessed by intention-to-treat analyses.Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side effects reported (nausea, vomiting, light headedness, urgency of micturition, facial flushing) were significantly more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of needing respiratory support (RR 1.16, 95% CI 1.03 to 1.29, three trials, 1969 infants), and of having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, three trials, 1969 infants). Only three trials provided data on childhood follow-up, and while one trial suggested poorer outcomes for infants who were exposed to prenatal TRH, the other two trials, that assessed infants using an established developmental instrument, showed no clear differences between groups in follow-up outcomes.Sensitivity analyses by trial quality, or subgroups with differing times from entry to birth, or different dose regimens of TRH, did not change these findings. AUTHORS' CONCLUSIONS: Prenatal TRH in addition to corticosteroids, given to women at risk of preterm birth, does not improve infant outcomes and can cause maternal side effects.

Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests.

Pituitary apoplexy occurs as a very rare complication of the pituitary function test. We have experienced two cases of pituitary apoplexy following anterior pituitary function tests for preoperative assessment: a triple bolus test and a TRH test. To elucidate such a rare complication, we outline our two cases and review 28 cases from the literature. The clinical characteristics, etiology, pathophysiology, and diagnostic and therapeutic implications are also discussed. The combined data suggest that pituitary function tests have the potential to precipitate pituitary apoplexy, and its manifestations range from a clinically benign event to a catastrophic presentation with permanent neurological deficits or even death, although most patients may fortunately have a good outcome. We suggest that the pituitary function test should not be done as a routine test, and when such a test is planned, the patient should be observed with caution for any symptomatic changes for at least 2 hours following the test for appropriate treatment. Further, MRI, especially enhanced studies, may provide an earlier diagnosis of the pituitary apoplexy since CT scan images often fail to demonstrate either density changes or obvious enlargement of the pituitary adenoma at the acute stage.

Alteration of regional cerebral blood flow to thyrotropin-releasing hormone therapy in acute encephalitis and encephalopathy during childhood.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is now used as a therapeutic agent for various neurological disorders. Animal study has shown that TRH was attributable to increased cerebral blood flow (CBF). AIMS: There have been occasional reports that TRH therapy was effective for improving symptoms of persistent disturbance of consciousness after acute encephalitis or encephalopathy during childhood. To determine whether TRH has an effect on increasing CBF to patients who have consciousness disturbance caused by acute encephalitis or encephalopathy, and to determine the optimal method of administration. METHODS: Sixteen patients aged 0.7-10.9 years (mean age, 3.2+/-3.1 years) who presented with persistent disturbance of consciousness resulting from acute encephalitis or encephalopathy and were treated with TRH. Regional CBF (rCBF) was measured by single photon emission computed tomography before and after TRH therapy. The alteration rates of rCBF were compared between the divided two groups concerning the dose levels, dosing periods, and treatment lags. RESULTS: The alteration rates of rCBF of the high dose group were higher than those of the low dose group. Differences in the dosing periods and treatment lags did not cause any significant difference of the alteration rates of rCBF. CONCLUSION: The study showed that higher alteration rates of the CBF were observed in the higher dosing group, and TRH have the potency of increasing CBF. TRH therapy would have the potential for effective treatment of persistent consciousness disturbance caused by childhood acute encephalitis or encephalopathy.

Effect of TRH on the development of ischemic cardiac arrhythmias in cats.

Acute experiments on cats showed that intravenous injection of thyrotropin-releasing hormone prevented blood pressure drop and produced a pronounced antiarrhythmic effect.

Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease?

Unfortunately, surfactant therapy is not routinely available to infants in some parts of the world because of its cost. It is the hypothesis of this article that in situations where surfactant is not available, there may be a role for antenatal thyrotropin-releasing hormone (TRH) plus glucocorticoid therapy. Data from randomized clinical trials, which compared therapy with antenatal glucocorticoid plus TRH to that with glucocorticoid alone were extracted and subjected to meta-analysis. The trials that incorporated surfactant therapy were analyzed separately from those in which surfactant was not used. In addition, because surfactant therapy was only available to some patients in the Australian ACTOBAT trial, each group analysis was performed with and without the ACTOBAT data. A characteristic of the earlier presurfactant trials is that few were designed for "intention to treat" analysis. In most of these studies, it was decided a priori to include babies who delivered within a specified time period after hormone therapy. The addition of TRH did not decrease respiratory distress syndrome in those trials in which surfactant therapy was used. In the presurfactant trials, respiratory distress syndrome was significantly decreased when "intention to treat" data were examined, as well as in those infants who delivered between 1 and 10 days after maternal therapy. There was also a significant decrease in oxygen dependency at 28 days after birth, and in oxygen dependency or death at this time, in those infants who delivered 1 to 10 days after treatment. Antenatal TRH had no significant effect of on neonatal complications such as air leak, intraventricular hemmorhage, patent ductus arteriosus, retinopathy of prematurity, or necrotizing enterocolitis. However, TRH did produce transient suppression of the pituitary thyroid axis. There were also a variety of transient complications in the mothers, including nausea, vomiting or flushing, light-headed feeling, and increased blood pressure. The authors conclude that the implementation of appropriate antenatal glucocorticoid treatment is the first priority. Once this has been established, the data presented here suggest that addition of antenatal TRH should be considered in those situations where surfactant is not available.

Pituitary apoplexy probably due to TRH and GnRH stimulation tests in a patient with acromegaly.

Pituitary apoplexy is the most serious and life-threatening complication of pituitary adenomas. Most of the cases occur spontaneously but it may occur also after a number of events such as the pituitary stimulation tests. We report a case of acromegaly due to a giant pituitary adenoma in which pituitary apoplexy developed 88 hours after TRH/GnRH stimulation test. The patient had severe headaches, nausea, vomiting, visual disturbance and mental alteration and the computed tomography (CT) scans revealed intratumoral and intraventricular bleeding. The pituitary mass was removed by transsphenoidal approach. The patient developed pneumonia and died on the 9th postoperative day. Pituitary apoplexy was confirmed at surgery and on histological examination. Immunohistochemical staining was positive for GH and PRL. This case indicates that pituitary apoplexy may develop several days after TRH/GnRH stimulation test.

Transient headache and impaired vision after intravenous thyrotropin-releasing hormone in a patient with pituitary macroadenoma.

We report a case of transient headache and impaired vision following administration of intravenous thyrotropin-releasing hormone (TRH) to a woman with a non-functioning pituitary macroadenoma, visual field defect, and elevated thyroid-stimulating hormone (TSH). The symptoms lasted for two hours and then resolved without known sequelae. There are a few other reported cases of similar adverse reactions to neuroendocrine manipulation in patients with pituitary macroadenomas. This is the second reported case of such adverse reactions to TRH alone and the first in which the patient had prior elevation of TSH.

Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

BACKGROUND: Pulmonary disease is common in preterm infants, despite antenatal glucocorticoid therapy. The addition of antenatal thyrotropin-releasing hormone therapy has been reported to decrease pulmonary morbidity in these infants. METHODS: We enrolled 996 women at 13 North American centers who were in preterm labor at <30 weeks' gestation in a double-blind, placebo-controlled, randomized trial of antenatal thyrotropin-releasing hormone, given intravenously in four doses of 400 microg each at eight-hour intervals. The primary outcome was chronic lung disease or death of the infant on or before the 28th day after delivery, and secondary outcomes were respiratory distress syndrome and chronic lung disease or death at 36 weeks' postmenstrual age. Complete data were available for 981 women and their 1134 live-born infants. The 769 infants born at < or = 32 weeks' gestation were defined as the group at risk. RESULTS: There were no significant differences between the at-risk treatment and placebo groups in mean (+/-SD) birth weight (1109+/-354 vs. 1097+/-355 g), gestational age (27.9+/-2.1 vs. 27.9+/-2.1 weeks), sex, or race. The frequencies of respiratory distress syndrome (66 percent vs. 65 percent), death at 28 days (11 percent vs. 11 percent), chronic lung disease or death at 28 days (45 percent vs. 42 percent) and at 36 weeks (32 percent vs. 34 percent), and other neonatal complications as well as the severity of lung disease were not significantly different in the at-risk treatment and placebo groups. Similarly, there were no differences in outcome between the treatment and placebo groups for the infants born at >32 weeks' gestation. CONCLUSIONS: In preterm infants at risk for lung disease, antenatal administration of thyrotropin-releasing hormone and glucocorticoid is no more beneficial than glucocorticoid alone.

[Effect of combined administration of TRH and dexamethasone in pregnant women and the course of their pregnancy]. / Vliv kombinovaného podávání TRH a dexametazonu na tehotné zeny a samotný prubeh jejich tehotenství.

UNLABELLED: Extremely immature neonates are threatened during the first days after delivery by many conditions which are due to incomplete development.--A key role is played during the first days of extrauterine life by the incidence and degree of the respiratory distress syndrome (RDS). Its incidence in neonates born before the completed 32nd week of gestation is very common. Causal treatment of RDS is not known. To overcome it the neonatologist must use in the majority of infants invasive techniques of controlled ventilation which are associated with the risk of further complications such as barotrauma, retinopathy and later the development of bronchopulmonary dysplasia. Attempts to influence intrauterine maturation of the lungs were started in the fifties. As a routine procedure nowadays corticoids are administered antenatally. Their limited effect divert the attention of perinatologists to other substances which could enhance maturation of pulmonary tissue. In human medicine ambroxol was introduced, in animals opiates are tested as well as beta-mimetics, aminophylline. The greatest hopes were aroused by trials with the use of T-hormones. T-hormones have a maturating regulating function in the foetal organism. They have an affinity for pneumocytes and in animal experiments they have a positive effect on surfactant formation. Moreover they act synergically when combined with corticoids. OBJECTIVE OF STUDY: a) to evaluate the safety of the method from the aspect of undesirable side-effects of hormone administration to the mother b) evaluation of hormone levels: TSH, total T4, total T3, TRH and prolactin in maternal serum.

Effect of antenatal thyrotropin-releasing hormone on uterine contractility, blood pressure, and maternal heart rate.

OBJECTIVE: The goal was to study the effects on uterine contractility, blood pressure, and heart rate of thyrotropin-releasing hormone given antenatally in combination with glucocorticoids to accelerate fetal maturation. STUDY DESIGN: A placebo-controlled, randomized, double-blind study was performed involving 30 women whose pregnancies were followed up at the University Hospital Gasthuisberg in 1994 and 1995. RESULTS: Thyrotropin-releasing hormone induced a significant mean increase of nearly 6 mm Hg in systolic blood pressure and approximately 5 mm Hg in diastolic blood pressure. The duration of this raise was < 20 minutes. Thyrotropin-releasing hormone had no significant effect on maternal heart rate or uterine contractility: 4.2 +/- 1.6 contractions per hour before versus 4.7 +/- 1.7 contractions per hour after treatment. CONCLUSIONS: Thyrotropin-releasing hormone induces a small (mean < 6 mm Hg) and brief mean (< 20 minutes) increase in blood pressure but appears to have no clinically detectable effect on uterine contractility.

Australian Collaborative Trial of Antenatal Thyrotropin-Releasing Hormone: adverse effects at 12-month follow-up. ACTOBAT Study Group.

OBJECTIVE: The Australian Collaborative Trial of Antenatal Thyrotropin-Releasing Hormone (ACTOBAT) assessed the efficacy of 200 microg of thyrotropin-releasing hormone (TRH) in combination with glucocorticoids in the prevention of neonatal lung disease. This paper reports the 12-month follow-up of the infants from the trial completed in 1994. DESIGN: This was a double-blinded randomized controlled trial. SETTING: Women were recruited from level 3 perinatal centers throughout Australia. PARTICIPANTS: Mothers who had not withdrawn from treatment and whose infants were discharged alive (1262 infants). Extensive efforts were made to trace this entire cohort. OUTCOME MEASURES: A questionnaire was mailed to parents for self-completion immediately before their baby's/babies' first birthday. The questionnaire included a checklist to assess sensory, motor, language, and social development, and use of health services. RESULTS: Milestone scores were developed from items on the follow-up form. Treatment with TRH was associated with an increased risk of motor delay, social delay, fine motor delay, sensory impairment, and early language impairment. No differences were seen between treatment and placebo groups for motor impairment. Multivariate analyses were performed, adjusting for chronological age, duration of gestation at randomization, time from randomization to delivery, parity, history of perinatal death, history of preterm rupture of the membranes, infant sex, singleton or twin status, maternal age, and maternal blood pressure (systolic and diastolic) at randomization. For the total cohort (N = 1022), treatment with TRH was associated with motor delay (odds ratio [OR], 1.51; 95% confidence interval [CI] 1.11 to 2.05); social delay (OR 1.40; 95% CI 1.01 to 1.95); sensory impairment (OR, 2.00; 95% CI 1.06 to 3.74); severe impairment (OR, 1.75; 95% CI 1.07 to 2.87); and a trend toward motor impairment (OR, 1.50; 95% CI .97 to 2.33), early language impairment (OR, 1.27, 95% CI .90 to 1.79), and fine motor delay (OR, 1.15; 95% CI .83 to 1.60). There were no differences between the treatment groups in hospital admissions (OR, 1.08; 95% CI .83 to 1.42), doctors' visits (general practitioner OR adj, 1.09; 95% CI .79 to 1.50 or specialist OR adj 1.15; 95% CI .87 to 1.49), respiratory symptoms (OR adj, 1.16; 95% CI .88 to 1.53), or behavioral disturbances (OR adj, .93; 95% CI .71 to 1.21). CONCLUSIONS: Because antenatal administration of TRH is associated with small, consistent deficits in major milestone achievements at 12 months of age, it is essential that additional planned trials make provision for long-term follow-up. Antenatal TRH should only be used in the context of a clinical trial.

Is maternal thyrotropin releasing hormone administration safe in the pregnant woman with preeclampsia?

Maternal intravenous administration of thyrotropin releasing hormone (TRH) is associated with rapid elevations of blood pressure potentially causative of cerebrovascular accidents. We report a case in which peak blood pressure of 220/120 mm Hg was attained from a baseline of 132/80 mm Hg following TRH administration in a preeclamptic patient.

Apoplexy of a pituitary macroadenoma as a severe complication of preoperative thyrotropin-releasing hormone (TRH) testing.

The case history of a 54-year-old male suffering from pituitary macroadenoma with suprasellar extension is reported. A TRH-test with 200 micrograms i.v. was followed by severe headache and vomiting after 60', and by development of ophthalmoplegia on the following day. Hyperdens patches on the CT scan showed haemorrhage into the tumor. A chromophobic adenoma with macroscopic and histological signs of haemorrhage was removed via the transsphenoidal route. In the postoperative period the ophthalmoplegia gradually disappeared but central hypoadrenia and hypothyroidism occurred. This is the second case in the literature showing that TRH alone and in a low dose may cause pituitary tumor apoplexy. It is concluded that TRH-testing is a risk for the patient with pituitary apoplexy. If, due to the size of the tumor the patients have to be operated on in any case, and the test is not of essential diagnostic value, the TRH-test should be done only in selected cases. Its use in the postoperative evaluation however is without risk for the patients.