Effect of dose rate and timing of administration of pegbovigrastim on white blood cell responses in grazing dairy cows.

Transition dairy cows experience a decline in immune function that increases the risk of peripartum disease. One strategy to improve peripartum immune function involves the use of a commercially available cytokine: bovine granulocyte-colony stimulating factor, with the addition of polyethylene glycol to increase duration of effectiveness. Treatment with Imrestor (15 mg pegbovigrastim; Elanco) one week before expected calving date (d -7) and again on the day of calving (d 0) was previously reported to increase the neutrophil number and improve neutrophil function; as a result, the incidence of clinical mastitis was reduced. We conducted 2 experiments over consecutive years to investigate the effect of a lower dose rate (half or quarter dose rate) of Imrestor in grazing dairy cattle and reduced administration frequency: one dose instead of the recommended 2. White blood cell counts were measured to determine changes in relative cell populations in response to treatment. Neutrophil function was assessed by measuring myeloperoxidase activity. Imrestor treatment increased the numbers of neutrophils, band cells, lymphocytes, and monocytes until 14 d postcalving in a dose-dependent manner; it also increased neutrophil myeloperoxidase activity. One dose of Imrestor increased white blood cell counts and myeloperoxidase activity, but the timing, degree, and duration of the response were different relative to the recommended 2 doses and were also dependent upon when Imrestor treatment was given. One dose at d -7 relative to expected calving date did not have a lasting effect postcalving, whereas one dose only on d 0 caused a delayed effect relative to cows that received 2 doses. There was no effect of Imrestor on milk yield or on blood indicators of transition cow health. A lower dose rate of Imrestor or a single dose of Imrestor on the day of calving may be sufficient to improve neutrophil function during the early postpartum in grazing dairy cows. Large-scale field studies are required to determine whether the smaller response from lower dose rates or the timing of the immunological response to drug delivery affect animal health in early lactation.

Losartan attenuates progression of osteoarthritis in the synovial temporomandibular and knee joints of a chondrodysplasia mouse model through inhibition of TGF-ß1 signaling pathway.

OBJECTIVE: Transforming growth factor beta 1 (TGF-ß1) is implicated in osteoarthritis (OA). The purpose of this study was to explore the ability of Losartan to inhibit the inflammatory signaling pathway of TGF-ß1 observed during osteoarthritic progression in the temporomandibular joint (TMJ) and knee joint using a genetic mouse model. METHODS: A murine OA model displaying the heterozygous chondrodysplasia gene (cho/+), a col11a1 mutation, was used to test this hypothesis. Following a 7-month treatment period with Losartan, the synovial joints were analyzed for histopathological improvement comparing two experimental groups. Tissues were fixed in paraformaldehyde, processed to paraffin section, and stained with Safranin O and Fast Green to visualize proteoglycans and collagen proteins in cartilage. Using the Modified Mankin scoring system, the degree of staining and OA progression were evaluated. RESULTS: Results show heterozygous animals receiving Losartan having diminished degeneration of TMJ condylar and knee joint articular cartilage. This was confirmed in the TMJ and knee by a statistically significant decrease in the Mankin histopathology score. Decreased expression of HtrA1, a key regulator to the TGF-ß1 signaling pathway, was demonstrated in vitro as well as in vivo, via Losartan inhibition. CONCLUSION: Using a genetic mouse model of OA, this study demonstrated the utility of Losartan to improve treatment of human OA in the TMJ and knee joint through inhibition of the TGF-ß1 signaling cascade. We further demonstrated inhibition of HtrA1, the lowering of Mankin scores to wild type control levels, and the limiting of OA progressive damage with treatment of Losartan.

Temporal and spatial water use on irrigated and nonirrigated pasture-based dairy farms.

Robust information for water use on pasture-based dairy farms is critical to farmers' attempts to use water more efficiently and the improved allocation of freshwater resources to dairy farmers. To quantify the water requirements of dairy farms across regions in a practicable manner, it will be necessary to develop predictive models. The objectives of this study were to compare water use on a group of irrigated and nonirrigated farms, validate existing water use models using the data measured on the group of nonirrigated farms, and modify the model so that it can be used to predict water use on irrigated dairy farms. Water use data were collected on a group of irrigated dairy farms located in the Canterbury, New Zealand, region with the largest area under irrigation. The nonirrigated farms were located in the Manawatu region. The amount of water used for irrigation was almost 52-fold greater than the amount of all other forms of water use combined. There were large differences in measured milking parlor water use, stock drinking water, and leakage rates between the irrigated and nonirrigated farms. As expected, stock drinking water was lower on irrigated dairy farms. Irrigation lowers the dry matter percentage of pasture, ensuring that the amount of water ingested from pasture remains high throughout the year, thereby reducing the demand for drinking water. Leakage rates were different between the 2 groups of farms; 47% of stock drinking water was lost as leakage on nonirrigated farms, whereas leakage on the irrigated farms equated to only 13% of stock drinking water. These differences in leakage were thought to be related to regional differences rather than differences in irrigated versus nonirrigated farms. Existing models developed to predict milking parlor, corrected stock drinking water, and total water use on nonirrigated pasture-based dairy farms in a previous related study were tested on the data measured in the present research. As expected, these models performed well for nonirrigated dairy farms but provided poor predictive power for irrigated farms. Partial least squares regression models were developed specifically to simulate corrected stock drinking water, milking parlor water, and total water use on irrigated dairy farms.

Water use on nonirrigated pasture-based dairy farms: Combining detailed monitoring and modeling to set benchmarks.

Water use in intensively managed, confinement dairy systems has been widely studied, but few reports exist regarding water use on pasture-based dairy farms. The objective of this study was to quantify the seasonal pattern of water use to develop a prediction model of water use for pasture-based dairy farms. Stock drinking, milking parlor, and total water use was measured on 35 pasture-based, seasonal calving dairy farms in New Zealand over 2 yr. Average stock drinking water was 60 L/cow per day, with peak use in summer. We estimated that, on average, 26% of stock drinking water was lost through leakage from water-distribution systems. Average corrected stock drinking water (equivalent to voluntary water intake) was 36 L/cow per day, and peak water consumption was 72 L/cow per day in summer. Milking parlor water use increased sharply at the start of lactation (July) and plateaued (August) until summer (February), after which it decreased with decreasing milk production. Average milking parlor water use was 58 L/cow per day (between September and February). Water requirements were affected by parlor type, with rotary milking parlor water use greater than herringbone parlor water use. Regression models were developed to predict stock drinking and milking parlor water use. The models included a range of climate, farm, and milk production variables. The main drivers of stock drinking water use were maximum daily temperature, potential evapotranspiration, radiation, and yield of milk and milk components. The main drivers for milking parlor water use were average per cow milk production and milking frequency. These models of water use are similar to those used in confinement dairy systems, where milk yield is commonly used as a variable. The models presented fit the measured data more accurately than other published models and are easier to use on pasture-based dairy farms, as they do not include feed and variables that are difficult to measure on pasture-based farms.

Proopiomelanocortin interference in the measurement of adrenocorticotrophic hormone: a United Kingdom National External Quality Assessment Service study.

OBJECTIVE: It is recognized that measurement of ACTH-precursor peptides including proopiomelanocortin (POMC) has clinical utility in identifying the aetiology of Cushing's syndrome. Recent data have also demonstrated cross-reactivity of POMC in ACTH immunoassays used in clinical laboratories. The aim of this study was to assess the cross-reactivity of POMC in the main commercial immunoassays for ACTH and to survey the awareness of laboratory professionals to this potential interference. METHOD: To assess cross-reactivity, specimens containing ACTH and/or POMC were prepared by the UK National External Quality Assessment Service (UK NEQAS) [Edinburgh]. A separate interpretative exercise was also sent to participating laboratories. RESULTS: Eighty-seven laboratories measured 'total' ACTH (i.e. ACTH and/or POMC) in their assays. Cross-reactivity of POMC varied from a mean of 1·6-4·7% (reflected in a large percentage increase in measured ACTH of up to 261% due to POMC cross-reactivity) depending on the manufacturer. Major differences in the clinical interpretation of test results were observed in returned responses to the interpretative exercise. CONCLUSION: An appraisal of POMC cross-reactivity in currently available ACTH immunoassays has been achieved. Cross-reactivity was sufficient to detect ACTH precursors at concentrations that could be found in patients with ectopic ACTH syndrome. These data will assist laboratories in interpreting results when assessing the hypothalamic-pituitary-adrenal axis. Endocrinologists and laboratory professionals should be aware of the degree of cross-reactivity in ACTH immunoassay in order to minimize the risk of misinterpretation of results and/or potentially delayed treatment.

Supportive Care: An Indispensable Component of Modern Oncology.

The advent of new cancer therapies, alongside expected growth and ageing of the population, better survival rates and associated costs of care, is uncovering a need to more clearly define and integrate supportive care services across the whole spectrum of the disease. The current focus of cancer care is on initial diagnosis and treatment, and end of life care. The Multinational Association of Supportive Care in Cancer defines supportive care as 'the prevention and management of the adverse effects of cancer and its treatment'. This encompasses the entire cancer journey, and necessitates involvement and integration of most clinical specialties. Optimal supportive care can assist in accurate diagnosis and management, and ultimately improve outcomes. A national strategy to implement supportive care is needed to acknowledge evolving oncology practice, changing disease patterns and the changing patient demographic.

Long-term experience of pegvisomant therapy as a treatment for acromegaly.

AIMS: To evaluate the long-term efficacy and safety of pegvisomant as a treatment for acromegaly. DESIGN: Retrospective analysis of clinical and trial data from all patients treated with pegvisomant since 1997 at two centres with common protocols. RESULTS: Fifty-seven patients (age range 27-78 years) have been treated with pegvisomant since 1997 for up to 91 months (median 18 months). Before commencing pegvisomant, patients had an IGF-I above the upper limit of normal (ULN) of the age-related reference range (median 1.8 x ULN, range 1.2-4.1). Ninety-five per cent normalized IGF-I using a median dose of 15 mg daily (range 10 mg alternate day to 60 mg daily) with no influence of gender on dose requirement. Five patients had combination therapy with either somatostatin analogues (SSA) or cabergoline. Two patients initially controlled on 10 mg and 20 mg required dose increases (to 20 mg + 40 mg) over 24 months to reduce IGF-I. Twenty-seven patients stopped pegvisomant. Reasons included side-effects [abnormal liver function tests (LFTs)] and patient choice. Two patients developed elevated liver transaminases, which normalized on stopping pegvisomant. Patients had 6-12-monthly pituitary magnetic resonance imaging (MRI) scans. One patient had significant tumour size increase. CONCLUSION: This long-term experience in 57 patients indicates pegvisomant to be effective, safe and well-tolerated. Raised transaminases occurred within the first month of therapy in two patients, and tumour growth was seen in one patient (tumour was growing prior to pegvisomant). In two patients increasing doses of pegvisomant were required to keep IGF-I within the target range.

An early center of bovine husbandry in southeast Asia.

Non Nok Tha is a prehistoric site in northeast Thailand. The radiocarbon dates suggest that it was first occupied by at least 3500 B.C., and possibly as early as 5000 B.C. The deepest levels contain unexpectedly early evidence for rice cultivation and bronze casting. Multivariate and cultural analyses of the bovine bones suggest that the first inhabitants raised domesticated cattle. This is among the earliest evidence for bovine domestication known.

SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Acute management of the endocrine complications of checkpoint inhibitor therapy.

Immunotherapy treatment with checkpoint inhibitors (CPI) (CTLA-4 and PD-1 inhibitors) significantly improves survival in a number of cancers. Treatment can be limited by immune-mediated adverse effects including endocrinopathies such as hypophysitis, adrenalitis, thyroiditis and diabetes mellitus. If endocrinopathies (particularly hypocortisolemia) are not recognized early, they can be fatal. The diagnosis and management of endocrinopathies can be complicated by simultaneous multi-organ immune adverse effects. Here, we present Endocrine Emergency Guidance for the acute management of the endocrine complications of checkpoint inhibitor therapy, the first specialty-specific guidance with Endocrinology, Oncology and Acute Medicine input and endorsed by the Society for Endocrinology Clinical Committee. We present algorithms for management: endocrine assessment and management of patients in the first 24 hours who present life-threateningly unwell (CTCAE grade 3-4) and the appropriate management of mild-moderately unwell patients (CTCAE grade 1-2) presenting with features compatible with an endocrinopathy. Other important considerations in relation to hypohysitis and the maintenance of glucocorticoid therapy are discussed.

Complex history of dog (Canis familiaris) origins and translocations in the Pacific revealed by ancient mitogenomes.

Archaeological evidence suggests that dogs were introduced to the islands of Oceania via Island Southeast Asia around 3,300 years ago, and reached the eastern islands of Polynesia by the fourteenth century AD. This dispersal is intimately tied to human expansion, but the involvement of dogs in Pacific migrations is not well understood. Our analyses of seven new complete ancient mitogenomes and five partial mtDNA sequences from archaeological dog specimens from Mainland and Island Southeast Asia and the Pacific suggests at least three dog dispersal events into the region, in addition to the introduction of dingoes to Australia. We see an early introduction of dogs to Island Southeast Asia, which does not appear to extend into the islands of Oceania. A shared haplogroup identified between Iron Age Taiwanese dogs, terminal-Lapita and post-Lapita dogs suggests that at least one dog lineage was introduced to Near Oceania by or as the result of interactions with Austronesian language speakers associated with the Lapita Cultural Complex. We did not find any evidence that these dogs were successfully transported beyond New Guinea. Finally, we identify a widespread dog clade found across the Pacific, including the islands of Polynesia, which likely suggests a post-Lapita dog introduction from southern Island Southeast Asia.

GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

Identification of a novel human islet amyloid polypeptide beta-sheet domain and factors influencing fibrillogenesis.

Human islet amyloid polypeptide (hIAPP) accumulates as pancreatic amyloid in type 2 diabetes and readily forms fibrils in vitro. Investigations into the mechanism of hIAPP fibril formation have focused largely on residues 20 to 29, which are considered to comprise a primary amyloidogenic domain. In rodents, proline substitutions within this region and the subsequent beta-sheet disruption, prevents fibril formation. An additional amyloidogenic fragment within the C-terminal sequence, residues 30 to 37, has been identified recently. We have extended these observations by examining a series of overlapping peptide fragments from the human and rodent sequences. Using protein spectroscopy (CD/FTIR), electron microscopy and X-ray diffraction, a previously unrecognised amyloidogenic domain was localised within residues 8 to 20. Synthetic peptides corresponding to this region exhibited a transition from random coil to beta-sheet conformation and assembled into fibrils having a typical amyloid-like morphology. The comparable rat 8-20 sequence, which contains a single His18Arg substitution, was also capable of assembling into amyloid-like fibrils. Examination of peptide fragments corresponding to residues 1 to 13 revealed that the immediate N-terminal region is likely to have only a modulating influence on fibril formation or conformational conversion. The contributions of charged residues as they relate to the amyloid-forming 8-20 sequence were also investigated using IAPP fragments and by assessing the effects of pH and counterions. The identification of these principal amyloidogenic sequences and the effects of associated factors provide details on the IAPP aggregation pathway and structure of the peptide in its fibrillar state.

Bone Health and Pelvic Radiotherapy.

Survivors who have received pelvic radiotherapy make up many of the long-term cancer population, with therapies for gynaecological, bowel, bladder and prostate malignancies. Individuals who receive radiotherapy to the pelvis as part of their cancer treatment are at risk of insufficiency fractures. Symptoms of insufficiency fractures include pelvic and back pain and immobility, which can affect substantially quality of life. This constellation of symptoms can occur within 2 months of radiotherapy up to 63 months post-treatment, with a median incidence of 6-20 months. As a condition it is under reported and evidence is poor as to the contributing risk factors, causation and best management to improve the patient's bone health and mobility. As radiotherapy advances, chronic symptoms, such as insufficiency fractures, as a consequence of treatment need to be better understood and reviewed. This overview explores the current evidence for the effect of radiotherapy on bone health and insufficiency fractures and identifies what we know and where gaps in our knowledge lie. The overview concludes with the need to take seriously complaints of pelvic pain from patients after pelvic radiotherapy and to investigate and manage these symptoms more effectively. There is a clear need for definitive research in this field to provide the evidence-based guidance much needed in practice.

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years.

At the time of the publication of Geoffrey Harris's monograph on 'Neural control of the pituitary gland' 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980s and 1990s; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses have been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As the understanding of the control of GH secretion advanced, developments of treatments for GH axis disorders have evolved. Administration of pituitary-derived human GH was followed by the introduction of recombinant human GH in the 1980s, and, more recently, by long-acting GH preparations. For GH excess disorders, dopamine agonists were used first followed by SST analogues, and in 2005 the GH receptor blocker pegvisomant was introduced. This review will cover the evolution of these discoveries and build a picture of our current understanding of the hypothalamo-GH axis.

Formation of amyloid fibrils by peptides derived from the bacterial cold shock protein CspB.

Three peptides covering the sequence regions corresponding to the first two (CspB-1), the first three (CspB-2), and the last two (CspB-3) beta-strands of CspB, the major cold shock protein of Bacillus subtilis, have been synthesized and analyzed for their conformations in solution and for their precipitation behavior. The peptides are nearly insoluble in water, but highly soluble in aqueous solutions containing 50% acetonitrile (pH 4.0). Upon shifts of the solvent condition toward lower or higher acetonitrile concentrations, the peptides all form fibrils resembling those observed in amyloid associated diseases. These fibrils have been identified and characterized by electron microscopy, binding of the dye congo red, and X-ray fiber diffraction. Characterization of the peptides in solution by circular dichroism and NMR spectroscopy shows that the formation of these fibrils does not require specific preformed secondary structure in the solution state species. While the majority of the soluble fraction of each peptide is monomeric and unstructured, different types of structures including alpha-helical, beta-sheet, and random coil conformations are observed under conditions that eventually lead to fibril formation. We conclude that the absence of tertiary contacts under solution conditions where binding interactions between peptide units are still favorable is a crucial requirement for amyloid formation. Thus, fragmentation of a sequence, like partial chemical denaturation or mutation, can enhance the capacity of specific protein sequences to form such fibrils.

Direct 1H NMR evidence for conversion of beta-D-cellobiose to cellobionolactone by cellobiose dehydrogenase from Phanerochaete chrysosporium.

The alpha- and beta-anomers of D-cellobiose were resolved by 1H NMR spectroscopy. Addition of cellobiose dehydrogenase purified from the white-rot P. chrysosporium led to selective conversion of beta-D-cellobiose. The product was identical to cellobionolactone as synthesized from Ca-cellobionate. Overnight incubation of the product led to an altered NMR spectrum, which was also obtained by incubation of cellobionolactone. The new spectrum matched that for Ca-cellobionate. The instability of cellobionolactone explains the detection of cellobionic acid as product in earlier studies.

Preparation of synthetic human islet amyloid polypeptide (IAPP) in a stable conformation to enable study of conversion to amyloid-like fibrils.

Human synthetic islet amyloid polypeptide (hIAPP) is rapidly converted to beta-sheet conformation and fibrils in aqueous media. Optimal solubility conditions for hIAPP were determined by circular dichroism spectroscopy and transmission electron microscopy. hIAPP in trifluoroethanol or hexafluoro-2-isopropanol (HFIP) diluted in water or phosphate buffer (PB) exhibited random structure which was converted to beta-sheet and fibrils with time. hIAPP, solubilised in HFIP, filtered and lyophilised remained in stable random structure for up to 7 days in water; in PB, insoluble aggregates precipitated from which protofilaments and fibrils formed with time. This suggests that amorphous aggregates of hIAPP could initiate islet amyloidosis in vivo.

A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection.

BACKGROUND: Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. METHODS: HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. RESULTS: A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. CONCLUSIONS: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

The antimalarial agent mefloquine inhibits ATP-sensitive K-channels.

The aim of this study was to determine whether antimalarial agents inhibit ATP-sensitive potassium (K(ATP)) channels and thereby contribute to the observed side-effects of these drugs. Mefloquine (10 - 100 microM), but not artenusate (100 microM), stimulated insulin release from pancreatic islets in vitro. Macroscopic K(ATP) currents were studied in inside-out patches excised from Xenopus oocytes expressing cloned K(ATP) channels. Mefloquine (IC(50) approximately 3 microM), quinine (IC(50) approximately 3 microM), and chloroquine inhibited the pancreatic beta-cell type of K(ATP) channel Kir6.2/SUR1. Artenusate (100 microM) was without effect. Mefloquine and quinine also blocked a truncated form of Kir6.2 (Kir6. 2DeltaC36) when expressed in the absence of SUR1. The extent of block was similar to that observed for Kir6.2/SUR1 currents. Our results suggest that inhibition of the beta-cell K(ATP) channel accounts for the ability of quinoline-based antimalarial drugs to stimulate insulin secretion, and thereby produce hypoglycaemia. The results also indicate that quinoline-based antimalarial agents inhibit K(ATP) channels by interaction with the Kir6.2 subunit. This subunit is common to beta-cell, neuronal, cardiac, skeletal muscle, and some smooth muscle K(ATP) channels suggesting that K(ATP) channel inhibition may contribute to the other side effects of these drugs, which include cardiac conduction abnormalities and neuropsychiatric disturbances.

Phaeochromocytoma and Acromegaly: a unifying diagnosis.

UNLABELLED: A 52-year-old lady was referred after a 5 cm left adrenal mass was detected on computed tomography (CT) scanning. She was asymptomatic although was noted to have acromegalic facies. Blood pressure (BP) was normal but plasma normetanephrines were raised to 2.81 mmol/l (<1.09) and urinary normetadrenaline excretion 5.3 µmol/24 h (0-4.3). Adrenal biochemistry screen was otherwise normal. Metaiodobenzylguanidine (MIBG) scan demonstrated uptake in the adrenal lesion. Growth hormone (GH) nadir on oral glucose tolerance test (OGTT) was 2.2 ng/ml with an elevated IGF1 level of 435 ng/ml (72-215), confirming acromegaly biochemically. The remainder of the pituitary screen was normal. A magnetic resonance imaging (MRI) scan of the pituitary revealed an enlarged pituitary gland with a microadenoma/cyst of 2-3 mm in diameter. Alpha blockade was achieved with a titrated dose of phenoxybenzamine before a successful laparoscopic hand-assisted left adrenalectomy. Postoperative biochemical testing revealed a normal plasma normetanephrine level of 0.6 nmol/l (<1.09) and a metanephrine level of 0.35 nmol/l (<0.46 nmol/l). Nadir on OGTT was normal at 0.07 ng/ml with an IGF1 level within the reference range at 111 ng/ml (75-215). Histology demonstrated a well-circumscribed and encapsulated oval mass with microscopic features typical for a phaeochromocytoma. The sections stained strongly positive for GHRH in 20% of cells on immunocytochemistry. Genetic analysis showed no pathogenic mutation. This is a report of the rare condition of a phaeochromocytoma co-secreting GHRH resulting in clinical and biochemical acromegaly. Neuroendocrine tumours can stain positive for GHRH without coexisting acromegaly, but the resolution of patient symptoms and normalisation of serum GH and IGF1 levels following surgery imply that this was functional secretion. Pituitary surgery should be avoided in such cases. LEARNING POINTS: Incidental findings on imaging require thorough investigation to determine the presence of serious pathology.Acromegaly and phaeochromocytoma are rarely coincident in the same patient. If this occurs, co-secretion of GHRH from the phaeochromocytoma or the presence of underlying genetic abnormalities must be considered.Acromegaly is due to ectopic GHRH-secreting neuroendocrine tumours in <1% of cases, most commonly pancreatic or bronchial lesions.Co-secretion of GHRH from a phaeochromocytoma is extremely rare.In such cases, the pituitary gland may appear enlarged but pituitary surgery should be avoided and surgical treatment of the neuroendocrine tumour attempted.