Presentation Summaries

Ann McCormack - Management of Aggressive Pituitary Tumours

Aggressive pituitary tumours (APT), accounting for up to 10% of pituitary tumours, are invasive tumours displaying rapid tumour growth and/or resistance to medical therapy and typically require multiple surgeries and radiotherapy in an attempt to control tumour growth. Pituitary carcinoma (PC), defined by the documented presence of craniospinal or systemic metastatic disease, is rare found in just 0.2% of all pituitary tumours1. Even in recent times, the mortality rates of APT and PC are 28% and 43% respectively at 11 years post tumour diagnosis ref ESE survey2. Recognising the APT and involvement of an expert multidisciplinary team are crucial in improving outcomes. The first guidelines in this field were published in 2018 and have established temozolomide as standard of care and first line chemotherapy in the management of APT3. Other targeted therapies such as bevacizumab (VEGF inhibition) and pasireotide (SSTR inhibition) for aggressive prolactinomas also offer promise while early results particularly for dual agent immunotherapy are very encouraging. The opportunity to provide patients with tumour molecular screening opens opportunities for personalised approaches and enrolment into early phase clinical trials.

1 Dworakowska D, Grossman AB. Aggressive and malignant pituitary tumours:state-of-the-art. Endocr. Relat. Cancer. 2018, 25:R559-R575.

2 McCormack A et al. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol. 2018, 178: 265-276.

3 Raverot G et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018, 178: G1-G24.

Ashish Munsif - In the pits: A tale of an aggressive prolactinoma

Although dopamine agonist therapy is commonly utilised in treatment of prolactinomas, they may not yield the desired effect. This case will explore the difficulties in managing an aggressive prolactinoma and the benefits of multidisciplinary care. It follows the progress of a 16 year old male with recurrent disease and illustrates the complexities of management in these scenarios. The role of somatostatin analogues is explored, as an additional therapeutic option for aggressive pituitary macroprolactinomas. Their use is well documented in Acromegaly and Cushings Disease but may also have a role in this setting, dependent on tumour cell expression amongst other factors. 

Carmela Caputo - Challenges in the screening of diagnosis of Cushing’s disease.

From screening, diagnosis, management and long term follow-up, Cushing’s disease (CD) is arguably the most challenging of all the pituitary adenoma types in clinical practice. Guidelines do advise on who and how to optimally screen for Cushing’s syndrome (CS), and there are pathways for the further work up and for the differential diagnosis. However, it is clear that the reality of screening, diagnosing and confirming CS is fraught with difficulties in the most part due to discordant results and technical issues. This talk will use case examples to demonstrate a few (of many) issues I have encountered in my clinical practice which highlights the everyday challenges which I encounter in screening and diagnosing CD.

Christine O’Neill - Thyroid: TI-RADS and Bethesda - Nodule conundrums

Ultrasound and fine needle aspiration cytology remains the mainstay of thyroid nodule assessment. This talk will cover recent updates in ultrasound and cytology assessment including a comparison of commonly used scoring systems. Newer technologies that may refine the assessment of thyroid nodules will also be discussed. This talk will focus on current areas of controversy and their impact on clinical management.

Christina Jang - Hypothalamic Amenorrhoea: Challenging Estrogen replacement scenarios

Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea in young women and is particularly prevalent in situations of low energy availability such as anorexia and excessive exercise.  A number of neuroendocrine and metabolic abnormalities may be demonstrated in women with FHA.  This talk will discuss some of the pathogenic mechanisms underlying FHA, the long terms health consequences and management options.

David Henley - Assessment of the HPA axis

Cortisol, the effector hormone of the hypothalamic-pituitary-adrenal (HPA) axis is secreted in a complex manner, with a daily (circadian) rhythm subserved by an underlying pulsatile (ultradian) rhythm. This can make assessment of the integrity of the HPA axis challenging. In general, dynamic testing is used to determine if elevated levels are suppressible or if low levels are stimulated to a degree that indicates adequate hormone reserve. This presentation will briefly review the normal physiology of the HPA axis and then summarise the various tests used to evaluate hypo- and hyperfunctioning of the HPA axis and the various pitfalls and caveats associated with these tests.

Emily Brooks - Polyuria/Polydipsia

The polyuria‐polydipsia syndrome comprises three major conditions: primary polydipsia, central diabetes insipidus (DI) and nephrogenic DI. Differentiating between these entities accurately is crucial as treatment approaches differ, and inadequate or incorrect treatment may lead to severe complications. However, determining the diagnosis has been challenging in clinical practice. Although the indirect water deprivation test has been the gold standard for many decades, its overall diagnostic accuracy is only 70%,  and it is particularly poor for primary polydipsia (40%).1 Direct measurement of arginine vasopressin (AVP), or antidiuretic hormone (ADH), is technically challenging and has been of limited clinical utility. Copeptin, the C‐terminal segment of the AVP pro‐hormone, is produced in equimolar amounts to AVP2 and correlates well with plasma AVP and serum osmolality.3 Unlike AVP, copeptin is highly stable ex vivo, and easy to measure2. Copeptin now has an important role in the differentiation of polyuria and polydipsia. This presentation will provide an update on the syndrome of polyuria-polydipsia, including diagnosis and the role of plasma copeptin.

1.     Fenske W, Quinkler M, Lorenz D, et al. Copeptin in the differential diagnosis of the polyuria‐polydipsia syndrome ‐ revisiting the direct and indirect water deprivation tests. J Clin Endocrinol Metab. 2011; 96: 1506‐ 1515.

2.     Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006; 52(1): 112‐ 119.

3.     Balanescu S, Kopp P, Gaskill MB, Morgenthaler NG, Schindler C, Rutishauser J. Correlation of plasma copeptin and vasopressin concentrations in hypo‐, iso‐, and hyperosmolar States. J Clin Endocrinol Metab. 2011; 96(4): 1046‐ 1052.

Gudmundur Johannsson - Growth Hormone Replacement in Adults

Growth hormone (GH) deficiency (GHD) in adults with hypopituitarism is associated with premature atherosclerosis and increased cardiovascular mortality. Whether unreplaced GHD, underlying pituitary disorder or other pituitary hormone deficiencies is the cause is debated.

GH mediate its effects either directly through its own receptor or through endocrine and paracrine action of IGF-I. This includes protein anabolic action, lipolysis, upregulation of the LDL-receptor and increased endothelial generation of nitric oxide. The clinical effects of GH replacement therefore includes improved cardiometabolic risk profile with beneficial effects on lipids, body composition and reduced diastolic blood pressure and systemic inflammatory markers. Effects of GH replacement are sustained in long-term open treatment trials with duration of more than 10 years with a good safety profile. Available data show that adults receiving long-term GH replacement have normal risk of mortality and no increased risk in the recurrence rate of pituitary tumours and de-novo neoplasia. In order to simplify treatment, increased convenience and possible improve adherence long-acting GH have been developed.

Studies in patients with long-term GH replacement show better outcome than previously described in hypopituitary patients. Whether this is due to the GH replacement or improved overall management of pituitary patients remains to be show.

Michael Huo - Role of the gamma knife in pituitary tumour management

Stereotactic radiosurgery is a form of intracranial radiotherapy utilising highly-precise target localisation and imaging techniques, allowing for the delivery of high doses of radiation with millimetre (or even sub-millimeter) accuracy and a steep dose gradient to ensure maximal sparing of normal tissue. The Gamma Knife is a sub-specialised radiosurgery machine capable of sub-millimetre precision, and is the most proven method of delivering stereotactic radiosurgery worldwide. An overview of the role of Gamma Knife radiosurgery for pituitary tumours will be given. Topics covered will include: the technical background of stereotactic radiosurgery, the role of radiosurgery for different types of pituitary lesions, published data on outcomes, and example cases.

Nele Lenders - Case of adult Growth Hormone deficiency

Adult growth hormone deficiency is characterised by a constellation of features including increased adiposity, low bone mass, reduced muscle mass and exercise capacity, adverse cardiovascular profile and impaired quality of life. Optimal replacement of growth hormone is associated with substantial improvement of these parameters. Careful dose titration is important for ensuring efficacy and safety of treatment. Various clinical parameters are known to impact growth hormone replacement, including age, sex, body mass index, baseline growth hormone status and quality of life. Of particular note, in panhypopituitary patients, other pituitary hormone replacements impact dosing requirements. Various external factors give rise to challenges in dose titration, including heterogeneity in growth hormone and IGF-1 assays, subjectivity of growth hormone effects, patient compliance and lack of long-term outcome data to guide treatment.

In this talk, I will present the case of a 45-year-old woman with panhypopituitarism following hypophysectomy for recurrent Cushing’s disease, highlighting various clinical challenges associated with growth hormone replacement in the real world.

Samantha Hocking - Obesity Update: Where are we in 2021?

Obesity continues to increase in prevalence globally and in Australia. Currently, one third of the Australian adult population is living with obesity and it is projected that 16.9 million Australians will have overweight or obesity in 2025. Equity is an important issue with obesity rates being higher in more socially disadvantaged and geographically remote communities. There is a high demand for services to manage weight and improve health, however, stigma can be a major barrier to individuals accessing required care. Effective therapies for weight reduction are available and new therapies are in the pipeline. So in 2021, how can an endocrinologist help patients living with obesity reduce their weight to improve their health?

Sunita De Sousa - Management of prolactinomas; the physician’s perspective

Prolactinomas are the most common clinically relevant pituitary adenoma, accounting for approximately 60% of cases, and prolactinomas are one of the commonest subtypes of aggressive pituitary tumour/pituitary carcinoma. Prolactinomas also feature prominently in the familial pituitary tumour syndromes.

Unlike other pituitary adenomas that are typically managed surgically, the first-line treatment of prolactinomas is medical therapy in the form of dopamine agonists such as cabergoline and bromocriptine. Treatment with dopamine agonists is usually highly effective, and a subset of patients achieve normoprolactinaemia and sustained tumour resolution allowing successful treatment withdrawal. However, 5-10% of patients experience intolerable side effects and 10-20% never achieve normoprolactinaemia and/or adequate prolactinoma shrinkage. The side effect profile of dopamine agonists has traditionally focused on gastrointestinal and cardiovascular symptoms, but mounting evidence demonstrates that hyperprolactinaemic

Warrick Inder - Prescribing Adult Growth Hormone in Australia in 2021

In the late 1980s, studies emerged demonstrating benefits ofgrowth hormone (GH) replacement in GH deficient adults. Australia was one of the last western countries to have access to funded GH therapy for adults. In 2012, ESA and APEG formed a joint working group which enlisted support from all pharmaceutical companies marketing GH in Australia. Ultimately GH was PBS-listed in late 2018 for use in adults with severe GH deficiency. In 2021, the process to prescribe GH for adults has been streamlined and simplified. There are three PBS-subsidised GH brands in Australia, meaning a choice of different devices and dose incrementation. Potential patients with adult onset GH deficiency must be 18 year or older and have organic hypothalamic or pituitary disease. Adults with childhood onset GH deficiency must have a congenital, genetic or structural cause. GH deficiency requires confirmation using a glucagon stimulation test, an insulin tolerance test or arginine test. The initial application includes a completed Severe Growth Hormone Deficiency supporting information form, and can be submitted online at Health Professional online Services (HPOS) www.servicesaustralia.gov.au/hpos or mailed. Subsequent prescriptions can be completed online or via a phone authority 1800 700 270.

Marg Ng - ’Starting a Research Career' – Why? And how? Reflections from a clinical PhD

Although some advance trainees consider undertaking a PhD a natural progression after completion of their endocrine training, many are more cautious. This talk will outline reasons to consider undertaking (or not) a PhD and how to address challenges that occur along the way. Mark will share his own experience from conducting a RCT of 100 subjects and also snapshots from other PhD projects from his peers.

Annabelle Hayes - Challenges in dopamine agonist therapy

Prolactinoma is the most common pituitary adenoma. The mainstay of management is use of dopamine agonists which are highly successful in controlling hyperprolactinaemia, tumour size and restoring fertility for the vast majority of patients. Well described intolerances include dizziness, headache and gastrointestinal side effects. Perhaps an underappreciated effect when prescribed for prolactinoma is that of psychiatric complications, with respect to impulse control disorders, depression and psychosis. 

The case discussed will review the limitations of dopamine agonist therapy and the challenges of managing an aggressive prolactinoma from a mass effect and fertility standpoint without this tool.

Craniopharyngioma update - A/Prof Chris Yates

Although they are benign epithelial tumours, craniopharyngiomas are invasive and cause significant morbidity, including visual impairment, anterior pituitary hormone deficits, diabetes insipidus and hypothalamic dysfunction. Expertise in diagnostics and treatment impacts outcomes and prognosis. Radical resection should only be contemplated if it carries a low risk of hypothalamic injury and frequently management involves a combination of limited surgery and tailored radiotherapy. Endocrinologists must carefully assess and manage pituitary and hypothalmic dysfunction pre and postoperatively, which may be challenging due to neuropsychosocial complications of these tumours and the treatment. The identification of BRAF and CTNNB1 (β-catenin) mutations in papillary and adamantinomatous craniopharyngiomas, respectively, has raised hope that targeted therapies may have a role in improving the management of these tumours in the future.