Diagnosis and Treatment > Medication

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Ved Bhushan Arya Department of Paediatric Endocrinology, Variety Club Children’s Hospital, King’s College Hospital NHS Foundation Trust, London, UK

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Jennifer Kalitsi Department of Paediatric Endocrinology, Variety Club Children’s Hospital, King’s College Hospital NHS Foundation Trust, London, UK

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Ann Hickey Department of Neonatology, King’s College Hospital NHS Foundation Trust, London, UK

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Sarah E Flanagan Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK

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Ritika R Kapoor Department of Paediatric Endocrinology, Variety Club Children’s Hospital, King’s College Hospital NHS Foundation Trust, London, UK

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Summary

Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resulting in severe hyperglycaemia is extremely uncommon and not reported previously in the context of HH due to HNF4A mutation. We report a novel observation of exceptional diazoxide sensitivity in a patient with HH due to HNF4A mutation. A female infant presented with severe persistent neonatal hypoglycaemia and was diagnosed with HH. Standard doses of diazoxide (5 mg/kg/day) resulted in marked hyperglycaemia (maximum blood glucose 21.6 mmol/L) necessitating discontinuation of diazoxide. Lower dose of diazoxide (1.5 mg/kg/day) successfully controlled HH in the proband, which was subsequently confirmed to be due to a novel HNF4A mutation. At 3 years of age, the patient maintains age appropriate fasting tolerance on low dose diazoxide (1.8 mg/kg/day) and has normal development. Diagnosis in proband’s mother and maternal aunt, both of whom carried HNF4A mutation and had been diagnosed with presumed type 1 and type 2 diabetes mellitus, respectively, was revised to maturity-onset diabetes of young (MODY). Proband’s 5-year-old maternal cousin, also carrier of HNF4A mutation, had transient neonatal hypoglycaemia. To conclude, patients with HH due to HNF4A mutation may require lower diazoxide than other group of patients with HH. Educating the families about the risk of marked hyperglycaemia with diazoxide is essential. The clinical phenotype of HNF4A mutation can be extremely variable.

Learning points:

  • Awareness of risk of severe hyperglycaemia with diazoxide is important and patients/families should be accordingly educated.

  • Some patients with HH due to HNF4A mutations may require lower than standard doses of diazoxide.

  • The clinical phenotype of HNF4A mutation can be extremely variable.

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Peter Novodvorsky Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Ziad Hussein Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Muhammad Fahad Arshad Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Ahmed Iqbal Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Malee Fernando Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Alia Munir Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Sabapathy P Balasubramanian Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
Department of General Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Summary

Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’ is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20–2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6–6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6–6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic.

Learning points:

  • Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1–2% of cases from parathyroid carcinoma.

  • PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia.

  • Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’, ‘auto-parathyroidectomy’ or ‘parathyroid apoplexy’ is a very rare in clinical practice but has been previously reported in the literature.

  • In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.

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Kingsley Okolie National Health Coop, Canberra, Australian Capital Territory, Australia

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Daniel Chen St. Vincent’s Hospital, Darlinghurst, Sydney, New South Wales, Australia

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Raf Ghabrial University of Sydney Medical School, Sydney, New South Wales, Australia

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Robert Schmidli Canberra Hospital, Woden, Canberra, Australian Capital Territory, Australia

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Summary

Multinodular goitre is not associated with eye disease, unless in a rare case of Marine–Lenhart syndrome where it coexists with Grave’s disease. Therefore, other causes of exophthalmos need to be ruled out when the eye disease is seen in a patient with multinodular goitre. Confusion can arise in patients with features suggestive of Graves’ ophthalmopathy in the absence of thyroid-stimulating hormone receptor autoantibodies and no evidence of other causes of exophthalmos. We present a case of multinodular goitre in a patient with exophthalmos which flared up after iodine contrast-based study. A 61-year-old Australian presented with a pre-syncopal attack and was diagnosed with toxic multinodular goitre. At the same time of investigations, to diagnose the possible cause of the pre-syncopal attack, computerised tomographic (CT) coronary artery angiogram was requested by a cardiologist. A few days after the iodine contrast-based imaging test was performed, he developed severe eye symptoms, with signs suggestive of Graves’ orbitopathy. MRI of the orbit revealed features of the disease. Although he had pre-existing eye symptoms, they were not classical of thyroid eye disease. He eventually had orbital decompressive surgery. This case poses a diagnostic dilemma of a possible Graves’ orbitopathy in a patient with multinodular goitre.

Learning points:

  • Graves’ orbitopathy can occur in a patient with normal autothyroid antibodies. The absence of the thyroid antibodies does not rule out the disease in all cases.

  • Graves’ orbitopathy can coexist with multinodular goitre.

  • Iodine-based compounds, in any form, can trigger severe symptoms, on the background of Graves’ eye disease.

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Pedro Marques Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, UK

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Nicola Tufton Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, UK

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Satya Bhattacharya Hepatobiliary and Pancreatic Surgery Unit, The Royal London Hospital, London, UK

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Mark Caulfield Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Scott A Akker Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, UK

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Summary

Mineralocorticoid hypertension is most often caused by autonomous overproduction of aldosterone, but excess of other mineralocorticoid precursors can lead to a similar presentation. 11-Deoxycorticosterone (DOC) excess, which can occur in 11-β hydroxylase or 17-α hydroxylase deficiencies, in DOC-producing adrenocortical tumours or in patients taking 11-β hydroxylase inhibitors, may cause mineralocorticoid hypertension. We report a 35-year-old woman who in the third trimester of pregnancy was found to have a large adrenal mass on routine obstetric ultrasound. On referral to our unit, persistent hypertension and long-standing hypokalaemia was noted, despite good compliance with multiple antihypertensives. Ten years earlier, she had hypertension noted in pregnancy which had persisted after delivery. A MRI scan confirmed the presence of a 12 cm adrenal mass and biochemistry revealed high levels of DOC and low/normal renin, aldosterone and dehydroepiandrosterone, with normal catecholamine levels. The patient was treated with antihypertensives until obstetric delivery, following which she underwent an adrenalectomy. Histology confirmed a large adrenal cortical neoplasm of uncertain malignant potential. Postoperatively, blood pressure and serum potassium normalised, and the antihypertensive medication was stopped. Over 10 years of follow-up, she remains asymptomatic with normal DOC measurements. This case should alert clinicians to the possibility of a diagnosis of a DOC-producing adrenal tumours in patients with adrenal nodules and apparent mineralocorticoid hypertension in the presence of low or normal levels of aldosterone. The associated diagnostic and management challenges are discussed.

Learning points:

  • Hypermineralocorticoidism is characterised by hypertension, volume expansion and hypokalaemic alkalosis and is most commonly due to overproduction of aldosterone. However, excess of other mineralocorticoid products, such as DOC, lead to the same syndrome but with normal or low aldosterone levels.

  • The differential diagnosis of resistant hypertension with low renin and low/normal aldosterone includes congenital adrenal hyperplasia, syndrome of apparent mineralocorticoid excess, Cushing’s syndrome, Liddle’s syndrome and 11-deoxycorticosterone-producing tumours.

  • DOC is one intermediate product in the mineralocorticoid synthesis with weaker activity than aldosterone. However, marked DOC excess seen in 11-β hydroxylase or 17-α hydroxylase deficiencies in DOC-producing adrenocortical tumours or in patients taking 11-β hydroxylase inhibitors, may cause mineralocorticoid hypertension.

  • Excessive production of DOC in adrenocortical tumours has been attributed to reduced activity of the enzymes 11-β hydroxylase and 17-α hydroxylase and increased activity of 21-α hydroxylase.

  • The diagnosis of DOC-producing adrenal tumours is challenging because of its rarity and poor availability of DOC laboratory assays.

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Ana Gonçalves Ferreira Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Tiago Nunes da Silva Endocrinology Department, Portuguese Institute of Oncology Francisco Gentil, Lisbon, Portugal

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Sofia Alegria Cardiology Department, Garcia de Orta Hospital, Almada, Portugal

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Maria Carlos Cordeiro Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Jorge Portugal Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Summary

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that can secrete catecholamines. The authors describe a challenging case who presented as stress cardiomyopathy and myocardial infarction (MI). A 76-year-old man, with a medical history of Parkinson’s disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and a previous inferior MI in 2001, presented to the emergency department due to chest pain, headaches and vomiting. He also reported worsening blood glucose levels and increasing constipation over the preceding weeks. BP was 185/89 mmHg (no other relevant findings). EKG had ST segment depression in leads V2-V6, T troponin was 600 ng/L (<14) and the echocardiogram showed left ventricular hypokinesia with mildly compromised systolic function. Nevertheless, he rapidly progressed to severe biventricular dysfunction. Coronary angiogram showed a 90% anterior descendent coronary artery occlusion (already present in 2001), which was treated with angioplasty/stenting. In the following days, a very labile BP profile and unexplained sinus tachycardia episodes were observed. Because of sustained severe constipation, the patient underwent an abdominal CT that revealed a retroperitoneal, heterogeneous, hypervascular mass on the right (62 × 35 mm), most likely a paraganglioma. Urinary metanephrines were increased several fold. 68Ga-DOTANOC PET-CT scan showed increased uptake in the abdominal mass (no evidence of disease elsewhere). He was started on a calcium-channel blocker and alpha blockade and underwent surgery with no major complications. Eight months after surgery, the patient has no evidence of disease. Genetic testing was negative for known germline mutations. This was a challenging diagnosis, but it was essential for adequate cardiovascular stabilization and to reduce further morbidity.

Learning points:

  • PPGL frequently produces catecholamines and can manifest with several cardiovascular syndromes, including stress cardiomyopathy and myocardial infarction.

  • Even in the presence of coronary artery disease (CAD), PPGL should be suspected if signs or symptoms attributed to catecholamine excess are present (in this case, high blood pressure, worsening hyperglycaemia and constipation).

  • Establishing the correct diagnosis is important for adequate treatment choice.

  • Inodilators and mechanical support might be preferable options (if available) for cardiovascular stabilization prior to alpha blockade and surgery.

  • Laboratory interference should be suspected irrespective of metanephrine levels, especially in the context of treated Parkinson’s disease.

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Michelle Maher Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Mohammed Faraz Rafey Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland

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Helena Griffin Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Katie Cunningham Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Francis M Finucane Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland

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Summary

A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team.

Learning points:

  • Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss.

  • Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up.

  • For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option.

  • Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary.

  • In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.

Open access
H Joshi Department of Endocrinology, Peterborough City Hospital, Peterborough, UK

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M Hikmat Department of Endocrinology, Peterborough City Hospital, Peterborough, UK

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A P Devadass Department of Histopathology, Addenbrookes Hospital, Cambridge, UK

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S O Oyibo Department of Endocrinology, Peterborough City Hospital, Peterborough, UK

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S V Sagi Department of Endocrinology, Peterborough City Hospital, Peterborough, UK

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Summary

IgG4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition which can affect various organs including the pituitary gland. The true annual incidence of this condition remains widely unknown. In addition, it is unclear whether IgG4 antibodies are causative or the end result of a trigger. With no specific biomarkers available, the diagnosis of IgG4-related hypophysitis remains a challenge. Additionally, there is a wide differential diagnosis. We report a case of biopsy-proven IgG4-related hypophysitis in a young man with type 2 diabetes mellitus.

Learning points:

  • IgG4-related hypophysitis is part of a spectrum of IgG4-related diseases.

  • Clinical manifestations result from anterior pituitary hormone deficiencies with or without diabetes insipidus, which can be temporary or permanent.

  • A combination of clinical, radiological, serological and histological evidence with careful interpretation is required to make the diagnosis.

  • Tissue biopsy remains the gold standard investigation.

  • Disease monitoring and long-term management of this condition is a challenge as relapses occur frequently.

Open access
Vasileios Chortis Institute of Metabolism and Systems Research, University of Birmingham
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

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Christine J H May Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

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Kassiani Skordilis Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Cellular Pathology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

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John Ayuk Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

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Wiebke Arlt Institute of Metabolism and Systems Research, University of Birmingham
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Departments of Endocrinology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

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Rachel K Crowley St. Vincent’s University Hospital and University College Dublin, Dublin, Ireland

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Summary

Context

Adrenal incidentalomas (AI) represent an increasingly common problem in modern endocrine practice. The diagnostic approach to AIs can be challenging and occasionally reveals surprising features. Here we describe two rare cases of complex adrenal lesions consisting of phaeochromocytomas with synchronous metastases from extra-adrenal primaries.

Case descriptions

Patient 1 – a 65-year-old gentleman with a newly diagnosed malignant melanoma was found to harbour an adrenal lesion with suspicious radiographic characteristics. Percutaneous adrenal biopsy was consistent with adrenocortical adenoma. After excision of the skin melanoma and regional lymphatic metastases, he was followed up without imaging. Three years later, he presented with abdominal discomfort and enlargement of his adrenal lesion, associated with high plasma metanephrines. Adrenalectomy revealed a mixed tumour consisting of a large phaeochromocytoma with an embedded melanoma metastasis in its core. Patient 2 – a 63-year-old lady with a history of NF-1-related phaeochromocytoma 20 years ago and previous breast cancer presented with a new adrenal lesion on the contralateral side. Plasma normetanephrine was markedly elevated. Elective adrenalectomy revealed an adrenal tumour consisting of chromaffin cells intermixed with breast carcinoma cells.

Conclusions

Adrenal incidentalomas require careful evaluation to exclude metastatic disease, especially in the context of a history of previous malignancy. Adrenal biopsy provides limited and potentially misleading information. Phaeochromocytomas are highly vascularised tumours that may function as a sieve, extracting and retaining irregularly shaped cancer cells, thereby yielding adrenal masses with intriguing dual pathology.

Learning points:

  • Adrenal incidentalomas require careful evaluation focused on exclusion of underlying hormone excess and malignant pathology.

  • Adrenal biopsy can be misleading and should only be considered in select cases.

  • Phaeochromocytomas harbouring intratumoural metastases from other, extra-adrenal primary malignancies represent rare pathological entities that highlight the complexities that can be presented by adrenal tumours.

Open access
Catherine D Zhang Departments of Internal Medicine, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Pavel N Pichurin Departments of Clinical Genomics, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Aleh Bobr Departments of Laboratory Medicine and Pathology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Melanie L Lyden Departments of Surgery, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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William F Young Jr Departments of Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Irina Bancos Departments of Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Summary

Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by spotty pigmentation of the skin and mucosa in association with various non-endocrine and endocrine tumors, including primary pigmented nodular adrenocortical disease (PPNAD). A 20-year-old woman was referred for suspected Cushing syndrome. She had signs of cortisol excess as well as skin lentigines on physical examination. Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. Unenhanced computed tomography scan of the abdomen did not reveal an obvious adrenal mass. She subsequently underwent bilateral laparoscopic adrenalectomy, and histopathology was consistent with PPNAD. Genetic testing revealed a novel frameshift pathogenic variant c.488delC/p.Thr163MetfsX2 (ClinVar Variation ID: 424516) in the PRKAR1A gene, consistent with clinical suspicion for CNC. Evaluation for other clinical features of the complex was unrevealing. We present a case of PPNAD-associated Cushing syndrome leading to the diagnosis of CNC due to a novel PRKAR1A pathogenic variant.

Learning points:

  • PPNAD should be considered in the differential for ACTH-independent Cushing syndrome, especially when adrenal imaging appears normal.

  • The diagnosis of PPNAD should prompt screening for CNC.

  • CNC is a rare multiple neoplasia syndrome caused by inactivating pathogenic variants in the PRKAR1A gene.

  • Timely diagnosis of CNC and careful surveillance can help prevent potentially fatal complications of the disease.

Open access
Yoko Olmedilla Endocrinology and Nutrition Service, Gregorio Marañón General Universitary Hospital, Madrid, Spain

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Shoaib Khan Oxford Centre for Endocrinology, Diabetes and Metabolism, Churchill Hospital, Oxford, UK

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Victoria Young Departments of Neuroradiology, John Radcliffe Hospital, Oxford, UK

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Robin Joseph Departments of Neuroradiology, John Radcliffe Hospital, Oxford, UK

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Simon Cudlip Departments of Neurosurgery, John Radcliffe Hospital, Oxford, UK

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Olaf Ansgorge Departments of Neuropathology, John Radcliffe Hospital, Oxford, UK

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Ashley Grossman Oxford Centre for Endocrinology, Diabetes and Metabolism, Churchill Hospital, Oxford, UK

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Aparna Pal Oxford Centre for Endocrinology, Diabetes and Metabolism, Churchill Hospital, Oxford, UK

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Summary

A 21 year-old woman was found to have a pituitary macroadenoma following an episode of haemophilus meningitis. Biochemical TSH and GH excess was noted, although with no clear clinical correlates. She was treated with a somatostatin analogue (SSA), which restored the euthyroid state and controlled GH hypersecretion, but she re-presented with a further episode of cerebrospinal fluid (CSF) leak and recurrent meningitis. Histology following transsphenoidal adenomectomy revealed a Pit-1 lineage plurihormonal adenoma expressing GH, TSH and PRL. Such plurihormonal pituitary tumours are uncommon and even more unusual to present with spontaneous bacterial meningitis. The second episode of CSF leak and meningitis appears to have been due to SSA therapy-induced tumour shrinkage, which is not a well-described phenomenon in the literature for this type of tumour.

Learning points:

  • Pit-1 lineage GH/TSH/PRL-expressing plurihormonal pituitary adenomas are uncommon. Moreover, this case is unique as the patient first presented with bacterial meningitis.

  • Inmunohistochemical plurihormonality of pituitary adenomas does not necessarily correlate with biochemical and clinical features of hormonal hypersecretion.

  • Given that plurihormonal Pit-1 lineage adenomas may behave more aggressively than classical pituitary adenomas, accurate pathological characterization of these tumours has an increasing prognostic relevance.

  • Although unusual, a CSF leak and meningitis may be precipitated by SSA therapy of a pituitary macroadenoma via tumour shrinkage.

Open access