Browse

You are looking at 1 - 10 of 55 items for :

  • Publication Details x
  • Country of Treatment x
  • Related Disciplines x
  • Unique/unexpected symptoms or presentations of a disease x
Clear All
Alessandra Mangone Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

Search for other papers by Alessandra Mangone in
Google Scholar
PubMed
Close
,
Quratulain Yousuf University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK

Search for other papers by Quratulain Yousuf in
Google Scholar
PubMed
Close
,
Wiebke Arlt Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

Search for other papers by Wiebke Arlt in
Google Scholar
PubMed
Close
,
Alessandro Prete Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

Search for other papers by Alessandro Prete in
Google Scholar
PubMed
Close
,
Fozia Shaheen Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

Search for other papers by Fozia Shaheen in
Google Scholar
PubMed
Close
,
Senthil-kumar Krishnasamy Walsall Healthcare NHS Trust, Walsall, UK

Search for other papers by Senthil-kumar Krishnasamy in
Google Scholar
PubMed
Close
,
Yasir S Elhassan Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

Search for other papers by Yasir S Elhassan in
Google Scholar
PubMed
Close
, and
Cristina L Ronchi Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology and Diabetes, University Hospital of Wurzburg, Wurzburg, Germany

Search for other papers by Cristina L Ronchi in
Google Scholar
PubMed
Close

Summary

The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion.

Learning points

  • Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection.

  • Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team.

  • Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.

Open access
Omayma Elshafie Department of Endocrinology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

Search for other papers by Omayma Elshafie in
Google Scholar
PubMed
Close
,
Samir Hussein Department of Radiology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman

Search for other papers by Samir Hussein in
Google Scholar
PubMed
Close
,
Moza Al Kalbani Department of Gynaecology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

Search for other papers by Moza Al Kalbani in
Google Scholar
PubMed
Close
,
Aisha Al Hamadani Department of Pathology

Search for other papers by Aisha Al Hamadani in
Google Scholar
PubMed
Close
,
Abir Bou Khalil Department of Endocrinology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

Search for other papers by Abir Bou Khalil in
Google Scholar
PubMed
Close
, and
Nicholas Woodhouse Department of Endocrinology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman

Search for other papers by Nicholas Woodhouse in
Google Scholar
PubMed
Close

Summary

A 33-year-old female presented in 2013 with left flank pain. Ultrasound and MRI pelvis showed a complex mass 9 × 7 cm arising from the left ovary suggestive of ovarian torsion. She underwent a laparoscopic cystectomy, but the patient was lost to follow-up. Three years later, she presented with abdominal distension. Ultrasound and CT scan revealed a solid left ovarian mass with ascites and multiple peritoneal metastasis. Investigations showed elevated CA 125, CA 19-9. Ovarian malignancy was suspected. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy on November 2016. The histopathology confirmed a well-differentiated thyroid cancer of ovarian origin with features of a papillary follicular variant without evidence of ovarian cancer and the thyroglobulin (Tg) level was elevated, more than 400 consistent with the diagnosis of malignant struma ovarii. The follow-up post-surgery showed normalization of CA 125, CA 19-9 and Tg. The patient underwent total thyroidectomy on January 2017. The histology was benign excluding thyroid cancer metastases to the ovary. She was started on thyroxine suppression, following which she received two ablation doses 131iodine (131I) each 5.3 GBq. The Tg remains slightly elevated at less than 10. 131I WBS showed no residual neck uptake and no distant avid metastasis. She was planned for molecular analysis which may indicate disease severity. We describe a case of malignant struma ovarii with widespread metastatic dissemination and a good response to surgery and 131I treatment without recurrence after 5 years of follow-up. The Tg remains slightly elevated indicating minimal stable residual disease.

Learning points

  • Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.

  • Presentation may mimic advanced carcinoma of the ovary.

  • Predominant sites of metastasis are adjacent pelvic structures.

  • Thyroidectomy and 131iodine therapy should be considered. The management should be similar to that of metastatic thyroid cancer.

Open access
Iris Dirven Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

Search for other papers by Iris Dirven in
Google Scholar
PubMed
Close
,
Bert Bravenboer Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

Search for other papers by Bert Bravenboer in
Google Scholar
PubMed
Close
,
Steven Raeymaeckers Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

Search for other papers by Steven Raeymaeckers in
Google Scholar
PubMed
Close
, and
Corina E Andreescu Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

Search for other papers by Corina E Andreescu in
Google Scholar
PubMed
Close

Summary

The Covid-19 vaccination has been rapidly implemented among patients with cancer. We present two cases of patients with endocrine tumours who developed lymphadenopathy following a Covid-19 vaccination. In the case of a patient with multiple endocrine neoplasia (MEN) 1 syndrome, an 18-fluorodeoxyglucose (18FDG)-PET/CT showed positive axillary lymph nodes. Further work-up with fine needle aspiration showed a reactive pattern following a Covid-19 vaccination in the ipsilateral arm shortly before the 18FDG-PET/CT. A second patient, in follow-up for thyroid cancer, developed clinical supraclavicular lymphadenopathy after a Covid-19 vaccination. Follow-up ultrasound proved the lesion to be transient. These cases demonstrate lymphadenopathy in response to a Covid-19 vaccination in two patients susceptible to endocrine tumours and metastatic disease. With growing evidence about the pattern and occurrence of lymphadenopathy after mRNA Covid-19 vaccination, recommendations for scheduling and interpretation of imaging among cancer patients should be implemented to reduce equivocal findings, overdiagnosis, and overtreatment, while maintaining a good standard of care in oncological follow-up.

Learning points

  • Reactive lymphadenopathy is very common after an mRNA vaccination against Covid-19 and should be part of the differential diagnosis in patients with endocrine tumours who recently received a Covid-19 mRNA vaccination and present with an ipsilateral lymphadenopathy.

  • A good vaccine history is essential in assessing the risk for lymphadenopathy and if possible, screening imaging in patients with endocrine tumours should be postponed at least 6 weeks after the previous vaccination.

  • For now, a multidisciplinary care approach is recommended to determine the necessary steps in the diagnostic evaluation of lymphadenopathy in the proximity of a Covid-19 vaccination.

Open access
Jenny S W Yun Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Jenny S W Yun in
Google Scholar
PubMed
Close
,
Chris McCormack Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Chris McCormack in
Google Scholar
PubMed
Close
,
Michelle Goh Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Michelle Goh in
Google Scholar
PubMed
Close
, and
Cherie Chiang Department of Internal Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
University of Melbourne, Parkville, Victoria, Australia

Search for other papers by Cherie Chiang in
Google Scholar
PubMed
Close

Summary

Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.

Learning points

  • Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.

  • Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.

  • AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.

  • Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.

  • Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.

Open access
Eugénie Van Mieghem Department of Internal Medicine, GZA Hospitals, Antwerpen, Belgium

Search for other papers by Eugénie Van Mieghem in
Google Scholar
PubMed
Close
,
Valent Intan-Goey Department of Internal Medicine, GZA Hospitals, Antwerpen, Belgium

Search for other papers by Valent Intan-Goey in
Google Scholar
PubMed
Close
,
Wendi Buffet Department of Pathological Anatomy, GZA Hospitals, Antwerpen, Belgium
Department of Pathological Anatomy, ZNA Hospitals, Antwerpen, Belgium

Search for other papers by Wendi Buffet in
Google Scholar
PubMed
Close
,
Martin Lammens Department of Pathological Anatomy, University Hospital of Antwerp, Edegem, Belgium

Search for other papers by Martin Lammens in
Google Scholar
PubMed
Close
,
Pieter Van Loo Department of Neurosurgery, GZA Hospitals, Antwerpen, Belgium

Search for other papers by Pieter Van Loo in
Google Scholar
PubMed
Close
, and
Pascale Abrams Department of Endocrinology, GZA Hospitals, Antwerpen, Belgium

Search for other papers by Pascale Abrams in
Google Scholar
PubMed
Close

Summary

Pituitary carcinoma is a rare type of malignancy and only accounts for 0.1–0.2% of all pituitary tumours. Most pituitary carcinomas are hormonally active and they are mostly represented by corticotroph and lactotroph carcinomas. Corticotroph carcinoma can present as symptomatic Cushing’s disease or can evolve from silent corticotroph adenoma which is not associated with clinical or biochemical evidence of hypercortisolism. We hereby present a case of a bone-metastasized corticotroph pituitary carcinoma masquerading as an ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with a history of a non-functioning pituitary macro-adenoma. Our patient underwent two transsphenoidal resections of the primary pituitary tumour followed by external beam radiation therapy. Under hydrocortisone substitution therapy she developed ACTH-dependent hypercortisolism without arguments for recurrence on pituitary MRI and without central-to-peripheral ACTH-gradient on inferior petrosal sinus sampling, both suggesting ectopic production. Ultimately, she was diagnosed with an ACTH-secreting vertebral metastasis originating from the primary pituitary tumour. This case report demonstrates the complex pathophysiology of pituitary carcinoma and the long diagnostic work-up. Certain features in pituitary adenoma should raise the suspicion of malignancy.

Learning points

  • The diagnosis of pituitary carcinoma can only be made based on documented metastasis, therefore, due to the often long latency period between the detection of the primary tumour and the occurrence of metastasis, the diagnostic work-up most often spans over multiple years.

  • Pituitary carcinoma including corticotroph carcinoma is very rare in contrast to pituitary adenoma and only accounts for 0.1–0.2% of all pituitary tumours.

  • Histopathology in pituitary adenoma should certainly accomplish the following goals: accurate tumour subtyping and assessment of tumoural proliferative potential.

  • Repeated recurrence of pituitary adenoma after surgical resection, a discrepancy between biochemical and radiological findings, resistance to medical and radiation therapy, and silent tumours becoming functional are all hallmarks of pituitary carcinoma.

  • Silent corticotroph adenomas are non-functioning pituitary adenomas that arise from T-PIT lineage adenohypophyseal cells and that can express adrenocorticotropic hormone on immunohistochemistry, but are not associated with biochemical or clinical evidence of hypercortisolism. Silent corticotroph adenomas exhibit a more aggressive clinical behaviour than other non-functioning adenomas.

  • Treatment options for corticotroph carcinoma include primary tumour resection, radiation therapy, medical therapy, and chemotherapy. Sometimes bilateral adrenalectomy is necessary to achieve sufficient control of the cortisol excess.

Open access
David Kishlyansky Division of Internal Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Search for other papers by David Kishlyansky in
Google Scholar
PubMed
Close
,
Gregory Kline Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Search for other papers by Gregory Kline in
Google Scholar
PubMed
Close
,
Amita Mahajan Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Search for other papers by Amita Mahajan in
Google Scholar
PubMed
Close
,
Konstantin Koro Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada

Search for other papers by Konstantin Koro in
Google Scholar
PubMed
Close
,
Janice L Pasieka Divison of Endocrine surgery, Surgical Oncology and Endocrinology, Department of Surgery, University of Calgary, Calgary, Alberta, Canada

Search for other papers by Janice L Pasieka in
Google Scholar
PubMed
Close
, and
Patrick Champagne Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada

Search for other papers by Patrick Champagne in
Google Scholar
PubMed
Close

Summary

An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing’s syndrome (CS) in 5.2% of cases reported in the literature. We present a previously healthy 43-year-old woman admitted to our hospital with cushingoid features and hypertensive urgency (blood pressure = 200/120 mmHg). Her 24-h urinary free cortisol was >4270 nmol/day (reference range (RR) = 100–380 nmol/day) with a plasma ACTH of 91.5 pmol/L (RR: 2.0–11.5 pmol/L). Twenty-four-hour urinary metanephrines were increased by 30-fold. Whole-body CT demonstrated a 3.7-cm left adrenal mass with a normal-appearing right adrenal gland. Sellar MRI showed a 5-mm sellar lesion. MIBG scan revealed intense uptake only in the left adrenal mass. She was managed pre-operatively with ketoconazole and phenoxybenzamine and underwent an uneventful left laparoscopic adrenalectomy, which resulted in biochemical resolution of her hypercortisolemia and catecholamine excess. Histology demonstrated a PCC (Grading System for Adrenal Pheochromocytoma and Paraganglioma score 5) with positive ACTH staining by immunohistochemistry. A PCC gene panel showed no mutations and there has been no evidence of recurrence at 24 months. This case highlights the difficult nature of localizing the source of CS in the setting of a co-existing PCC and sellar mass.

Learning points

  • An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC) is an important item to be considered in all patients presenting with ectopic Cushing’s syndrome (CS).

  • In exceptionally rare cases, patients with ectopic CS may present with multiple lesions, and a systematic approach considering all potential sources is crucial to avoid misdiagnosis.

  • CS with a large adrenal mass but lacking contralateral adrenal atrophy should raise suspicion of an ACTH-dependent process.

  • In patients with clinical suspicion of PCC, clinicians should be mindful of the use of steroids and beta-blockers without appropriate alpha blockade as they may precipitate an adrenergic crisis.

Open access
Jay Nguyen Lincoln Memorial University-DeBusk College of Osteopathic Medicine, Harrogate, Tennessee, USA

Search for other papers by Jay Nguyen in
Google Scholar
PubMed
Close
and
Dennis Joseph Endocrinology Center of Lake Cumberland, Somerset, Kentucky, USA

Search for other papers by Dennis Joseph in
Google Scholar
PubMed
Close

Summary

Autonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule’s malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed suspicious sonographic features and fine-needle aspiration was ‘suspicious for malignancy’. The patient underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Most reports of TSHR I568T mutation have been seen in patients with benign thyroid conditions. While there is insufficient data to suggest that the TSHR I568T mutation causes aggressive thyroid malignancy, we believe clinicians who identify the presence of this mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.

Learning points

  • Germline and somatic activating mutations in the genes coding for the thyroid-stimulating hormone receptor (TSHR) have been frequently reported in familial and sporadic autonomous thyroid adenomas and non-autoimmune hyperthyroidism.

  • Most reports of TSHR I568T mutation have been detected in patients with benign thyroid conditions.

  • We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation and subsequently underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma.

  • Clinicians who identify the presence of TSHR I568T mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.

Open access
Adrian Po Zhu Li Department of Endocrinology ASO/EASO COM, King ’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

Search for other papers by Adrian Po Zhu Li in
Google Scholar
PubMed
Close
,
Sheela Sathyanarayan Department of Endocrinology ASO/EASO COM, King ’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

Search for other papers by Sheela Sathyanarayan in
Google Scholar
PubMed
Close
,
Salvador Diaz-Cano Departments of Cellular Pathology and Molecular Pathology, Queen Elizabeth Hospital, Birmingham, UK
Division of Cancer Studies, King’s College London, London, UK

Search for other papers by Salvador Diaz-Cano in
Google Scholar
PubMed
Close
,
Sobia Arshad Department of Endocrinology ASO/EASO COM, King ’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

Search for other papers by Sobia Arshad in
Google Scholar
PubMed
Close
,
Eftychia E Drakou Department of Clinical Oncology, Guy’s Cancer Centre – Guy’s and St Thomas’ NHS Foundation Trust, Great Maze Pond, London, UK

Search for other papers by Eftychia E Drakou in
Google Scholar
PubMed
Close
,
Royce P Vincent Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

Search for other papers by Royce P Vincent in
Google Scholar
PubMed
Close
,
Ashley B Grossman Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK

Search for other papers by Ashley B Grossman in
Google Scholar
PubMed
Close
,
Simon J B Aylwin Department of Endocrinology ASO/EASO COM, King ’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

Search for other papers by Simon J B Aylwin in
Google Scholar
PubMed
Close
, and
Georgios K Dimitriadis Department of Endocrinology ASO/EASO COM, King ’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, Department of Diabetes, Faculty of Life Sciences, School of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK

Search for other papers by Georgios K Dimitriadis in
Google Scholar
PubMed
Close

Summary

A 49-year-old teacher presented to his general physician with lethargy and lower limb weakness. He had noticed polydipsia, polyuria, and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34 mmol/L) with hyperparathyroidism (parathyroid hormone: 356 ng/L) and hypokalaemia (K: 2.7 mmol/L) and was admitted for i.v. potassium replacement. A contrast-enhanced CT chest/abdomen/pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17 × 11 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2 cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process. His serum cortisol was 2612 nmol/L, and adrenocorticotrophic hormone was elevated at 67 ng/L, followed by inadequate cortisol suppression to 575 nmol/L from an overnight dexamethasone suppression test. His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10 L/24 h and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia, and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18flurodeoxyglucose-PET (FDG-PET) scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32 mm pancreatic uncinate process mass showed significant uptake. Genetic testing confirmed multiple endocrine neoplasia type 1.

Learning points

  • In young patients presenting with primary hyperparathyroidism, clinicians should be alerted to the possibility of other underlying endocrinopathies.

    In patients with multiple endocrine neoplasia type 1 (MEN-1) and ectopic adrenocorticotrophic hormone syndrome (EAS), clinicians should be alerted to the possibility of this originating from a neoplasm above or below the diaphragm.

  • Although relatively rare compared with sporadic cases, thymic carcinoids secondary to MEN-1 may also be associated with EAS.

  • Electrolyte derangement, in particular hypokalaemia and hypercalcaemia, can precipitate mild nephrogenic diabetes insipidus.

Open access
Said Darawshi Department of Endocrinology, Rambam Health Care Campus, Haifa, Israel
The Faculty of Medicine, Technion, Haifa, Israel

Search for other papers by Said Darawshi in
Google Scholar
PubMed
Close
,
Mahmoud Darawshi Clalit Health Services, Northern District – Arrabah, Israel

Search for other papers by Mahmoud Darawshi in
Google Scholar
PubMed
Close
, and
Deeb Daoud Naccache Department of Endocrinology, Rambam Health Care Campus, Haifa, Israel
The Faculty of Medicine, Technion, Haifa, Israel

Search for other papers by Deeb Daoud Naccache in
Google Scholar
PubMed
Close

Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis.

Learning points

  • Severe hypocalcaemia can a presenting symptom for breast cancer relapse.

Open access
Mark R Postma Department of Endocrinology, Medical Imaging Center

Search for other papers by Mark R Postma in
Google Scholar
PubMed
Close
,
Jos M A Kuijlen Department of Neurosurgery, Medical Imaging Center

Search for other papers by Jos M A Kuijlen in
Google Scholar
PubMed
Close
,
Astrid G W Korsten Department of Otorhinolaryngology-Head and Neck Surgery, Medical Imaging Center

Search for other papers by Astrid G W Korsten in
Google Scholar
PubMed
Close
,
Henriëtte E Westerlaan Department of Radiology, Medical Imaging Center

Search for other papers by Henriëtte E Westerlaan in
Google Scholar
PubMed
Close
,
Alfons C M van den Bergh Department of Radiation Oncology, University Medical Center Groningen, Groningen, the Netherlands

Search for other papers by Alfons C M van den Bergh in
Google Scholar
PubMed
Close
,
Janine Nuver Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands

Search for other papers by Janine Nuver in
Google Scholar
PubMed
Close
,
Wilfred F A den Dunnen Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands

Search for other papers by Wilfred F A den Dunnen in
Google Scholar
PubMed
Close
, and
Gerrit van den Berg Department of Endocrinology, Medical Imaging Center

Search for other papers by Gerrit van den Berg in
Google Scholar
PubMed
Close

Summary

In July 2017, a 35-year-old woman was referred to our care for treatment of a large pituitary mass with an unusually high growth rate. She presented with right-sided ptosis and diplopia (n. III palsy), increasing retrobulbar pain and vertigo. Although laboratory investigations were consistent with acromegaly, she exhibited no clear phenotypic traits. During transsphenoidal surgery aimed at biopsy, typical adenomatous tissue was encountered, upon which it was decided to proceed to debulking. Histopathological analysis demonstrated a poorly differentiated plurihormonal Pit-1-positive adenoma with focal growth hormone (GH) and prolactin positivity, positive SSTR2 staining and a Ki-67 of 20–30%. Postoperative magnetic resonance imaging (MRI) examination revealed a large tumour remnant within the sella invading the right cavernous sinus with total encasement of the internal carotid artery and displacement of the right temporal lobe. As a consequence, she was treated additionally with radiotherapy, and a long-acting first-generation somatostatin analogue was prescribed. Subsequently, the patient developed secondary hypocortisolism and diabetes mellitus despite adequate suppression of GH levels. In September 2019, her symptoms recurred. Laboratory evaluations indicated a notable loss of biochemical control, and MRI revealed tumour progression. Lanreotide was switched to pasireotide, and successful removal of the tumour remnant and decompression of the right optic nerve was performed. She received adjuvant treatment with temozolomide resulting in excellent biochemical and radiological response after three and six courses. Symptoms of right-sided ptosis and diplopia remained. Evidence for systemic therapy in case of tumour progression after temozolomide is currently limited, although various potential targets can be identified in tumour tissue.

Learning points

  • Poorly differentiated plurihormonal Pit-1-positive adenoma is a potentially aggressive subtype of pituitary tumours.

  • This subtype can express somatostatin receptors, allowing treatment with somatostatin analogues.

  • A multidisciplinary approach involving an endocrinologist, neurosurgeon, pituitary pathologist, neuroradiologist, radiation oncologist and medical oncologist is key for the management of patients with aggressive pituitary tumours, allowing the successful application of multimodality treatment.

  • Temozolomide is first-line chemotherapy for aggressive pituitary tumours and carcinomas.

  • Further development of novel targeted therapies, such as peptide receptor radionuclide therapy (PRRT), vascular endothelial growth factor (VEGF) receptor-targeted therapy, tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors and immune checkpoint inhibitors, is needed.