Julie Lynch

Pituitary dysfunction following cranial radiotherapy for adult‐onset nonpituitary brain tumours

There are limited data concerning the evolution of radiation‐induced hypopituitarism in adult‐onset brain tumour (AO‐BT) survivors, in part the consequence of the limited survival of many of these individuals. We aim to characterize the pituitary‐related outcomes following cranial radiotherapy (cXRT) for adult‐onset primary nonpituitary brain tumours.

Impaired quality of life in patients with treated acromegaly despite long-term biochemically stable disease: Results from a 5-years prospective study

Patients with acromegaly demonstrate impaired quality of life (QoL), but data on long‐term QoL changes in treated acromegaly are limited. This study evaluates and identifies factors that influence QoL in patients with long‐term biochemical remission.

The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications

Disturbances of coagulation and fibrinolysis are usually multifactorial and growing evidence suggests that endocrinopathies modulate the haemostatic balance. The thrombotic alterations in endocrine disorders range from mild laboratory clotting abnormalities with little clinical significance to serious thrombotic and bleeding disorders directly related to hormonal disturbances. This literature review focuses on presenting the current data on the effects of thyroid and pituitary disorders on various parameters of the haemostatic system. With the exception of overt hypothyroidism which appears to cause a bleeding tendency, the rest of the endocrinopathies discussed in this review (subclinical hypothyroidism, hyperthyroidism, endogenous hypercortisolaemia, growth hormone deficiency, acromegaly, prolactinoma/hyperprolactinaemia and hypogonadotrophic hypogonadism) are associated with a hypercoagulable and hypofibrinolytic state, increasing the overall cardiovascular risk and thromboembolic potential in these patients. In most studies, the haemostatic abnormalities seen in endocrine disorders are usually reversible with successful treatment of the underlying condition and biochemical disease remission. High‐quality studies on larger patient cohorts are needed to produce robust evidence on the effects of endocrine disorders and their therapeutic interventions on coagulation and fibrinolysis, as well as on the long‐term mortality and morbidity outcomes in association with endocrine‐related haemostatic imbalance. Given the rarity of some of the endocrine disorders, multicentre studies are required to achieve this target.

Lanreotide autogel in acromegaly - a decade on.

Introduction: The novel formulation of lanreotide, lanreotide (LAN) autogel (ATG), has been available in Europe since 2001 and USA from 2006 for the treatment of acromegaly. It is one of only two clinically available somatostatin analogs available for use in acromegaly. Data relating to the use of ATG in acromegaly, specifically relating to comparison to octreotide (OCT) LAR and patient acceptability and preference, have been slow to accumulate. Areas covered: We performed a comprehensive review of the original literature relating to development, pharmacokinetics, acceptability and clinical efficacy of ATG. Expert opinion: LAN ATG is a novel formulation of LAN consequent on self-assembly of nanotubules in water. Diffusion between molecules within the nanotubules and surrounding tissue fluid in vivo leads to pseudo first-order pharmacokinetics. Efficacy is equivalent to the alternate long-acting somatostatin analog, OCT LAR, normalizing growth hormone and IGF-I levels in around 60 and 50% respectively. Control of tumor growth is observed in over 95% of patients, with 64% seeing a clinically significant reduction in tumor size. ATG is provided in a prefilled syringe for deep subcutaneous injection, allowing self-injection, and may be administered up to 8 weeks greatly improving convenience for the patient. The data strongly support consideration of ATG as the medical therapy of choice for patients with acromegaly.

Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center

PurposeDAX-1 (NR0B1) is an orphan nuclear receptor, which plays a critical role in development and regulation of the adrenal gland and hypothalamo–pituitary–gonadal axis. Mutations in NR0B1 lead to adrenal hypoplasia congenita (AHC), hypogonadotropic hypogonadism (HH) and azoospermia in men. Presentation is typically with adrenal insufficiency (AI) during infancy or childhood. To date only eight cases/kindreds are reported to have presented in adulthood.MethodsWe describe two new cases of men with DAX-1 mutations who presented in adulthood and who were diagnosed at a large University Hospital.ResultsCase 1 presented with AI at 19 years. At 38 years he was diagnosed with HH. Detailed history revealed a brother diagnosed with AI at a similar age. Sequencing of the DAX-1 (NR0B1) gene revealed a heterozygous c.775T > C substitution in exon 1, which changes codon 259 from serine to proline (p.Ser259Pro). Case 2 was diagnosed with AI at 30 years. Aged 37 years he presented with HH and azoospermia. He was treated with gonadotropin therapy but remained azoospermic. Testicular biopsy showed maturational arrest and hypospermatogenesis. Analysis of the NR0B1 gene showed a heterozygous c.836C > T substitution in exon 1, resulting in a change of codon 279 from proline to leucine (p.Pro279Leu). This change alters the structure of the repression helix domain of DAX-1 and affects protein complex interactions with NR5A family members.ConclusionsWe describe two missense mutations within the putative carboxyl-terminal ligand binding domain of DAX-1, presenting with AHC and HH in adulthood, from a single center. DAX-1 mutations may be more frequent in adults than previously recognized. We recommend testing for DAX-1 mutations in all adults with primary AI and HH or impaired fertility where the etiology is unclear.

Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

Summary A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Learning points: Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly. Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion, mainly from neuroendocrine tumours of pancreatic or bronchial origin. Differentiating between acromegaly of pituitary origin and ectopic acromegaly can cause diagnostic challenges due to similarities in clinical presentation and biochemistry. Serum GHRH can be a useful diagnostic tool to diagnose ectopic acromegaly. Pituitary imaging is crucial to differentiate between a pituitary adenoma and pituitary hyperplasia, which is a common finding in ectopic acromegaly. Diagnosing ectopic acromegaly is pivotal to avoid unnecessary interventions to the pituitary and preserve normal pituitary function.