The value of plasma metanephrine measurements during adrenal vein sampling.

Objective: The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS. Design: This is a diagnostic accuracy study in a tertiary referral endocrinology department. Methods: Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS. Results: There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet-PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet-AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%). Conclusions: Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy. Significance statement: Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

The where, who and how of adrenal vein sampling in Australia and New Zealand.

INTRODUCTION: Primary aldosteronism (PA) causes 10-15% of cases of hypertension, and it is increasingly recognised as being under-diagnosed. An interventional radiology procedure, adrenal vein sampling (AVS), is a necessary and important diagnostic procedure for complete workup of PA. There is an anticipated increase in demand for AVS as detection of PA improves. This study aims to describe the current landscape of AVS in Australia and New Zealand (NZ). METHODS: Two surveys exploring AVS methodology and performance were conducted of (i) Endocrinology Unit Heads and (ii) interventional radiologists who perform AVS, at public hospitals with Endocrinology Units across Australia and NZ. RESULTS: Responses were received from 48/53 Endocrinology Unit Heads (91%) and 35 radiologists from 26 sites (87% of AVS sites). AVS was provided at 28/48 Endocrinology sites (58%) across Australia and NZ. In Australia, sites were concentrated in Victoria, New South Wales and Queensland with none in the Northern Territory; in NZ, sites were more evenly distributed across the North and South Islands. AVS was performed by 1-2 dedicated radiologists at 24 sites, 2-3 radiologists at two sites and a rotating roster of radiologists at two sites. Responses to both surveys revealed significant variation in AVS methodology and interpretation of AVS results. CONCLUSION: There is significant heterogeneity in the availability of AVS, the procedural details and the interpretation of results across Australia and NZ, which potentially impacts the quality of patient care and ability to scale up AVS capacity to meet increasing demand.

Characteristics and gender affirming healthcare needs of transgender and non-binary students starting hormone therapy in a student health service in Aotearoa New Zealand.

Introduction Traditionally, gender-affirming hormonal therapy (GAHT) is initiated in secondary care, but a primary care based approach has been developed to reduce access barriers. Aim We aim to describe the demographics, hormone choices, and additional referrals made for young people initiating GAHT in a primary care setting in Aotearoa New Zealand. Methods Clinical notes were reviewed for all patients who commenced GAHT between 1 July 2020 to the end of 2022 at a tertiary education health service. Data were collected on age, ethnicity, gender, type of hormones prescribed, and any additional referrals. Results Eighty five patients commenced GAHT during the review period (64% assigned male at birth and starting oestrogen-based GAHT, 36% assigned female at birth and commencing testosterone-based GAHT). Fourty seven percent of patients identified as transgender female, 38% as non-binary, and 15% as transgender male. Spironolactone was the most common choice of testosterone blocker (81%). The choice of oestrogen formulation was fairly equal between patches (54%) and tablets (46%). Eighty percent of those assigned male at birth chose to preserve fertility, 54% requested voice therapy, and 87% of those assigned female at birth requested top surgery. Discussion There is a need for improved understanding of non-binary gender-affirmation needs, in particular those of Maori and Pasifika youth. An informed consent approach in primary care can reduce barriers and distress for transgender youth seeking GAHT. The high unmet need for top surgery for transgender people assigned female at birth requires attention.

A contemporary clinical approach to genetic testing for heritable hyperparathyroidism syndromes.

PURPOSE: The improved access and affordability of next generation sequencing has facilitated the clinical use of gene panel testing to test concurrently patients for multiple heritable hyperparathyroidism syndromes. However, there is little guidance as to which patients should be selected for gene panel testing and which genes should be included in such panels. In this review, we provide a practical approach to considering, interpreting and managing genetic testing for familial primary hyperparathyroidism (PHPT) syndromes and familial hypocalciuric hypercalcaemia (FHH) in patients with PTH-dependent hypercalcaemia. We discuss known genes implicated in PHPT and FHH, testing criteria and yields, pre-test counselling, laboratory considerations, and post-test management. METHODS: In addition to reviewing the literature, we conducted audits of local genetic testing data to examine the real-world yield of genetic testing in patients with PTH-dependent hypercalcaemia. RESULTS: Our local audits revealed a positive genetic testing rate of 15-26% in patients with suspected hyperparathyroidism syndromes. CONCLUSION: Based on the particular testing criteria met, affected patients should be tested for variants in the genes currently implicated in PHPT (MEN1, CDC73, RET, CDKN1B, GCM2, CASR) and/or FHH (CASR, GNA11, AP2S1). Patients should be provided with pre- and post-test counselling, including consideration of potential implications for family members.

Primary hyperparathyroidism in adults-(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society.

OBJECTIVE: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions. RESULTS: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. CONCLUSIONS: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.

Primary hyperparathyroidism in adults-(Part II) surgical management and postoperative follow-up: Position statement of the Endocrine Society of Australia, The Australian & New Zealand Endocrine Surgeons, and The Australian & New Zealand Bone and Mineral Society.

OBJECTIVE: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions. RESULTS: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended. CONCLUSIONS: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism.

Primary lymph node gastrinoma: 2 cases and a review of the literature.

INTRODUCTION: Gastrinoma is a rare tumour of the diffuse neuroendocrine system with the primary invariability located within the duodenum or pancreas. Numerous authors have described gastrinoma apparently isolated to peripancreatic lymph nodes, following exhaustive radiological and operative localisation and examination. METHOD: Two cases of apparent primary lymph node gastrinoma seen in our institution are presented, along with a literature review including 58 other presented cases. RESULTS: On prolonged follow-up up to 131 months, 34 patients have remained in remission supporting the diagnosis of primary lymph node gastrinoma. Occult primary disease, usually in the form of microduodenal tumours, have become evident in the remaining 24 cases. CONCLUSION: The existence of primary lymph node gastrinoma is supported by many presented case studies, but long-term follow-up of all patients should occur in the expectation that occult primary disease will become apparent in some.

Therapeutic options in the management of obesity.

In New Zealand 28.4% of adults now classify as obese, whilst a total of 63.8% are overweight or obese (BMI >25 kg/m²). This presents an ever increasing social and economic burden to individuals, families and the healthcare system. Obesity is a major risk factor for cancer, cardiovascular, metabolic, and respiratory disorders. Preventing obesity is the optimal long-term population strategy and must be a government priority. There are many approaches which could be taken to facilitate this, however it is important not to forget those who are currently overweight or obese. This review addresses the current therapeutic options in the treatment of obesity, focusing on lifestyle changes, medications, and surgery in New Zealand. It also presents a suggested algorithm for the clinician assessing and managing obese patients in New Zealand.

Pathogenesis of the metabolic syndrome: insights from monogenic disorders.

Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

Multiple endocrine neoplasia type 1 (MEN1).

Multiple endocrine neoplasia type 1 (MEN1) is inherited in an autosomal dominant fashion and predisposes to the development of hyperplastic or neoplastic changes in the parathyroid and pituitary glands and the endocrine pancreas, along with numerous other characteristic tumors and features. The management of each entity differs to some degree from their sporadic counterparts, while the lack of a genotype-phenotype correlation requires lifelong clinical, biochemical and radiological screening for the development of new tumors. While the syndrome itself is relatively rare (a prevalence of 1-10/100 000), it is likely that health-care practitioners from numerous specialities will occasionally encounter a patient with MEN1 and therefore a basic knowledge of the syndrome is important. In addition, many of the associated tumors are seen commonly in sporadic form, and a judicious policy is therefore required in deciding how thoroughly patients who develop these tumors should be screened for MEN1. The current literature on MEN1 is reviewed and key learning points are suggested for the clinician.

Monogenic diabetes: a diagnostic algorithm for clinicians.

Monogenic forms of beta cell diabetes account for approximately 1%-2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables genetic counseling, and has implications for cascade screening of extended family members. We describe those types of monogenic beta cell diabetes which are recognisable by distinct clinical features and have implications for altered management; the cost effectiveness of making a genetic diagnosis in this setting; the use of complementary diagnostic tests to increase the yield among the vast majority of patients who will have commoner types of diabetes which are summarised in a clinical algorithm; and the vital role of cascade genetic testing to enhance case finding.

A cross-over study of the acute effects of espresso coffee on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus.

The objective was to determine the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Eighteen participants who were habitual coffee drinkers, were studied using a random-order cross-over design. After a fasting blood sample participants consumed either a double-shot black espresso coffee, decaffeinated coffee, or hot water. The main outcomes were area under the curve (AUC) glucose and insulin, and insulin sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT) performed one hour later. Other outcomes were change in glucose and insulin and also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was marginally different between beverages (P=.06) being greater following caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to 198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95% CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour following beverage consumption. There was a marginal difference in IGI between beverages (P=.097) with coffee having a lower incremental increase in insulin/glucose than water (P=.037) though no difference between coffee and decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso coffee in people with type 2 diabetes mellitus results in a marginally greater excursion of glucose during a following OGTT compared with water or decaffeinated coffee. This effect does not appear to be mediated by changes in insulin sensitivity.

Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy.

Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

Chimpanzee tool use for honey and termite extraction in Central Africa.

Observations are presented primarily from two study sites located in the extreme southwestern tip of the Central African Republic. The use of flexible stalks and rigid sticks to extract termites from mounds and pounding, prying, and digging tools to penetrate melipone, honey bee, and ground-dwelling bee hives by Pan t. troglodytes are documented or inferred from circumstantial evidence. Functionally, termite extraction tools were similar to other locations in west and central Africa, but the plant species used were considerably different. Extraction of bees using large pieces of wood as pounding tools has not been recorded elsewhere in wild chimpanzees. No environmental factor that differs between the east and west of the range of P. t. troglodytes that would cause the difference in tool use was identified. © 1994 Wiley-Liss, Inc.