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Featured researches published by Mark Sherlock.


Clinical Endocrinology | 2018

In women with PCOS, waist circumference is a better surrogate of glucose and lipid metabolism than disease status per se

Agnieszka Pazderska; Tommy Kyaw Tun; N. Phelan; Anne McGowan; Mark Sherlock; Lucy-Ann Behan; Gerard Boran; James Gibney

Cardiometabolic abnormalities are recognized in polycystic ovary syndrome (PCOS). However, over‐emphasis on PCOS as a risk factor potentially results in over‐investigation and treatment of some women with and under‐recognition of cardiometabolic risk in obese women without PCOS. Our objective was to explore the association between waist circumference (WC) and indices of glucose and lipid metabolism in women with and without PCOS.


Clinical Endocrinology | 2014

Spironolactone interference in the immunoassay of androstenedione in a patient with a cortisol secreting adrenal adenoma

Rachel K. Crowley; Deirdre Broderick; Triona O'Shea; Gerard Boran; Vincent Maher; Stephen Crowther; James Gibney; Kevin C. Conlon; Mark Sherlock

Sir, In the assessment of patients with secondary hypertension and an adrenal lesion, the endocrinologist seeks to establish what adrenal hormones are implicated in the patient’s increased blood pressure and whether the lesion could be malignant (adrenocortical carcinoma). Hypersecretion of steroids from two zones of the adrenal cortex is unusual in benign adrenal disease and may indicate that the lesion is an adrenocortical carcinoma. Such hormonal hypersecretion is not always clinically apparent; therefore, the managing physician is dependent upon measurement of steroid hormones by nonisotopic immunoassay or sometimes by radioimmunoassay (RIA). Steroid hormones share multiple structural similarities; cross-reaction of the RIA antibodies with other hormones is recognized but often dismissed as of little clinical significance. We present a case in which spironolactone interfered with androstenedione measurement, the result of which changed risk stratification for malignancy. A 48-year-old man was referred from Cardiology for investigation of hypokalaemic hypertension in association with an adrenal mass. At presentation, his blood pressure was 180/ 100 mmHg while taking olmesartan 20 mg, hydrochlorothiazide 25 mg, felodipine 5 mg and spironolactone 25 mg daily. Echocardiography revealed left ventricular hypertrophy. Serum potassium was 3 3 mM. Noncontrast CT demonstrated a 3 3 cm mass in the right adrenal gland with a mean attenuation of 26 Hounsfield units (HU) (Fig. 1). Endocrine investigations revealed increased plasma androstenedione (19 9, reference range 2 8– 10 5 nM), using the Direct Androstenedione Coat-a-Count radioimmunoassay method (Siemens Healthcare, Camberley, Surrey, UK). Plasma cortisol concentration (DPC Immulite 2000 System; Siemens Healthcare) at 0900 h was not suppressed at 159 nM after a 1 mg overnight dexamethasone suppression test (normal < 50 nM). Hypercortisolaemia was confirmed with a 48-h low-dose dexamethasone suppression test; cortisol was 263 nM (normal < 50 nM). Plasma ACTH concentration before dexamethasone was undetectable. Three 24-h urine collections for catecholamines and metanephrines, performed to exclude pheochromocytoma, were normal. The finding of increased androstenedione coupled with Hounsfield units of 26 on imaging raised concerns that this gentleman had an adrenocortical carcinoma with hypersecretion across two zones of the adrenal cortex (zona fasciculata and reticularis). However, spironolactone, hydrochlorothiazide and olmesartan were discontinued for assessment of renin–angiotensin–aldosterone system, and 6 weeks later he underwent re-assessment, at which time androstenedione measured 3 7 nM, and there was no evidence of primary hyperaldosteronism. This suggested that the initial result represented assay interference. The patient underwent laparoscopic adrenalectomy with postoperative glucocorticoid cover. Histological examination of the excised adrenal yielded a Weiss score of 0/9. Six weeks after surgery he underwent a short synacthen test (250 lg of Synacthen ; Alliance Pharmaceuticals, Chippenham, Wiltshire, UK) with a 30-min cortisol response of 366 nM (normal > 550 nM). The patient remains on oral glucocorticoid replacement therapy and will undergo serial re-assessment of the hypothalamic–pituitary adrenal axis. In this case, hypercortisolaemia with undetectable ACTH suggested Cushing’s syndrome of adrenal origin. The possibility of Fig. 1 CT abdomen demonstrating 3 3 cm right-sided adrenal adenoma (white arrow) and contralateral gland (black arrow).


Endocrinology, Diabetes & Metabolism Case Reports | 2016

Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia

T O’Shea; R K Crowley; M Farrell; S MacNally; P Govender; J Feeney; James Gibney; Mark Sherlock

Summary Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1u2009nmol/L (0–1.5u2009nmol) and 17-Hydroxyprogesterone >180u2009nmol/L (<6.5u2009nmol/L). CT abdomen was performed as the patient complained of rapid-onset increasing abdominal girth and revealed bilateral large adrenal myelolipomata. MRI brain revealed a large meningioma involving the right sphenoid wing with anterior displacement of the right eye and associated bony destruction. Surgical debulking of the meningioma was performed and histology demonstrated a meningioma, which stained positive for the progesterone receptor. Growth of meningioma has been described in postmenopausal women receiving hormone replacement therapy, in women receiving contraceptive therapy and in transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. Learning points: Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels. Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours. Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.


Endocrinology, Diabetes & Metabolism Case Reports | 2016

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome.

A Pazderska; Stephen Crowther; Pradeep Govender; Kevin C. Conlon; Mark Sherlock; James Gibney

Summary Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. Learning points AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous. Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention. Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing’s syndrome.


20th European Congress of Endocrinology | 2018

Hyperandrogenaemia in women with type 1 diabetes mellitus; associations with lipids and lipoprotein particle size, and early vascular disease

Anjuli Gunness; Agnieszka Pazderska; Mohamed Ahmed; Anne McGowan; Niamh Phelan; Gerard Boran; Angela Taylor; Wiebke Arlt; Kevin Moore; Behan Lucy Ann; Mark Sherlock; James Gibney


20th European Congress of Endocrinology | 2018

Pregnancy and acromegaly - clinical outcomes from the Irish Pituitary Network

Anne Marie Hannon; Rosemary Dineen; Aftab Khattak; Steven J. Hunter; Mark Sherlock; Christopher J. Thompson


Society for Endocrinology BES 2017 | 2017

Androgen excess is highly prevalent in women with idiopathic intracranial hypertension and is biochemically distinct from polycystic ovary syndromes

Catherine Hornby; Connar Westgate; Hannah Botfield; Keira Markey; James Mitchell; Carl Jenkinson; Lorna Gilligan; Mark Sherlock; James Gibney; Jeremy Tomlinson; Wiebke Arlt; Alexandra Sinclair


Age and Ageing | 2017

024Structuring Diabetes Mellitus Care in Long Term Nursing Home Residents

Donal Fitzpatrick; El Sayed Ibrahim; Sean Kennelly; Desmond O’Neill; Mark Sherlock


19th European Congress of Endocrinology | 2017

Androgen profiling by liquid chromatography-mass spectrometry (LC-MS) in reproductive-age women with and without diabetes

Anjuli Gunness; Agnieska Pazderska; Mohamed Ahmed; Niamh Phelan; Gerard Boran; Angela E. Taylor; Wiebke Arlt; Kevin Moore; Lucy-Ann Behan; Mark Sherlock; James Gibney


19th European Congress of Endocrinology | 2017

Dissecting the androgen excess phenotype of women with idiopathic intracranial hypertension

Catherine Hornby; Connar Westgate; Hannah Botfield; Keira Markey; Carl Jenkinson; Lorna Gilligan; Mark Sherlock; James Gibney; Jeremy Tomlinson; Wiebke Arlt; Alexandra Sinclair

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Wiebke Arlt

Queen Elizabeth Hospital Birmingham

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Michael Jeffers

Boston Children's Hospital

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Niamh Phelan

Boston Children's Hospital

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