Clinical Overview > Condition/ Syndrome > Hyperprolactinaemia

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Ilse C A Bakker Department of Internal Medicine, Section of Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands

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Chris D Schubart Department of Psychiatry, Tergooi Hospital, Hilversum, The Netherlands

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Pierre M J Zelissen Department of Internal Medicine, Section of Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands

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Summary

In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs.

Learning points

  • Prolactinoma coinciding with psychosis can represent a therapeutic challenge.

  • In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels.

  • Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis.

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Ahmed Iqbal Department of Diabetes and Endocrinology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield, S5 7AU, UK

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Peter Novodvorsky Department of Diabetes and Endocrinology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield, S5 7AU, UK

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Alexandra Lubina-Solomon Department of Diabetes and Endocrinology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield, S5 7AU, UK

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Fiona M Kew Department of Gynaecological Oncology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield, S10 2JF, UK

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Jonathan Webster Department of Diabetes and Endocrinology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield, S5 7AU, UK

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Summary

Secondary amenorrhoea and galactorrhoea represent a common endocrine presentation. We report a case of an oestrogen-producing juvenile granulosa cell tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following surgical resection of the tumour. This patient presented with a 9-month history of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l) were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with undetectable β-human chorionic gonadotropin. MRI showed a bulky pituitary with no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the right ovary with no evidence of metastatic disease. Serum inhibin B was elevated at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post-operatively, oestrogen and prolactin levels were normalised, and she subsequently had a successful pregnancy. In summary, we present a case of an oestrogen-secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical state analogous to pregnancy. To the best of our knowledge, this is the first report of hyperprolactinaemia as a result of excessive oestrogen production in the context of a JGCT.

Learning points

  • Hyperprolactinaemia with bilateral galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is not always caused by a prolactin secreting pituitary adenoma.

  • Significantly elevated serum oestradiol levels in the range seen in this case, in the absence of pregnancy, are indicative of an oestrogen-secreting tumour.

  • JGCTs are rare hormonally active ovarian neoplasms mostly secreting steroid hormones.

  • Serum inhibin can be used as a granulosa cell-specific tumour marker.

  • JGCTs have an excellent prognosis in the early stages of the disease.

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J Bukowczan Regional Pituitary Tumour Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK

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K Lois Regional Pituitary Tumour Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK

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M Mathiopoulou Regional Pituitary Tumour Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK

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A B Grossman Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, OX3 7LE, UK

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R A James Regional Pituitary Tumour Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK

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Summary

Giant prolactinomas are rare tumours of the pituitary, which typically exceed 40 mm in their largest dimension. Impairment of higher cognitive function has been noted post-operatively after transcranial surgery and as a long-term consequence of the radiotherapy treatment. However, there has been little that is reported on such disturbances in relation to the tumour per se, and to our knowledge, there has been none in terms of responsivity to dopamine agonist therapy and shrinkage in these tumours. We present a case of successful restoration of severely impaired cognitive functions achieved safely after significant adenoma involution with medical treatment alone.

Learning points

  • Giant prolactinomas can be present with profound cognitive defects.

  • Dopamine agonists remain in the mainstay first-line treatment of giant prolactinomas.

  • Mechanisms of the reversible cognitive impairment associated with giant prolactinoma treatment appear to be complex and remain open to further studies.

  • Young patients with giant prolactinomas mandate genetic testing towards familial predisposition.

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Lisa Burback Alberta Hospital Edmonton, Addiction and Mental Health Program, Alberta Health Services, 17480 Fort Road, Post Office Box 307, Edmonton, Alberta, Canada T5J 2J7

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Summary

A previously healthy 32-year-old woman developed cyclical mood swings after being prescribed cabergoline for a pituitary microprolactinoma. These mood swings persisted for over 2 years, at which point she developed an acute manic episode with psychotic features and was admitted to a psychiatry unit. Cabergoline was discontinued and replaced with aripiprazole 10 mg/day. Her manic episode quickly resolved, and she was discharged within 6 days of admission. The aripiprazole suppressed her prolactin levels for over 18 months of follow-up, even after the dose was lowered to 2 mg/day. There was no significant change in tumor size over 15 months, treatment was well tolerated. However, after 9 months of taking 2 mg aripiprazole, she developed brief manic symptoms, and the dose was returned to 10 mg daily, with good effect.

Learning points

  • Dopamine agonists such as cabergoline, which are a standard treatment for microprolactinomas, can have serious adverse effects such as psychosis or valvular heart disease.

  • Aripiprazole is a well-tolerated atypical antipsychotic that, unlike other antipsychotics, is a partial dopamine agonist capable of suppressing prolactin levels.

  • Adjunctive, low-dose aripiprazole has been utilized to reverse risperidone-induced hyperprolactinemia.

  • This case report demonstrates how aripiprazole monotherapy, in doses ranging from 2 to 10 mg/day, was effective in suppressing prolactin in a woman with a microprolactinoma who developed psychiatric side effects from cabergoline.

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K Majumdar University College London Hospitals NHS Foundation Trust, Diabetes and Endocrinology, 250 Euston Road, London NW1 2PG, UK

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M Barnard Whittington Hospital, London, UK

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S Ramachandra Whittington Hospital, London, UK

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M Berovic Whittington Hospital, London, UK

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M Powell National Hospital for Neurology and Neurosurgery, Neurosurgery, London, UK

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Summary

Tuberculosis (TB) is an important cause of mortality and morbidity across the world. In 2–5% of all cases of systemic TB, the C is affected, with lesions reported in the meninges, cortex and ventricles. Intrasellar tuberculomas, however, are extremely rare. We report the interesting case of a young female patient who presented with secondary hypothyroidism and hyperprolactinaemia. She was treated successfully for pituitary TB. We also highlight and discuss some interesting (and hitherto unreported) endocrine issues. Radiological and histological features and treatment of pituitary TB are discussed using this case as an example.

Learning points

  • Intrasellar TB continues to be a rare presentation, but incidence and prevalence are expected to grow with increasing numbers of multidrug-resistant TB and shrinking geographical boundaries across the world.

  • Pituitary TB can present with features of a typical adenoma, but has certain radiological and histological features that help to differentiate from an adenoma.

  • Patients can present with a variety of endocrine abnormalities at different times.

  • The presence of an intrasellar mass in individuals at a high risk of developing TB, or with a previous history of systemic TB, should prompt the diagnosis of pituitary TB. In such individuals, it may be worth considering a trial of anti-tuberculous therapy, before considering surgery.

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Gabriela Alejandra Sosa Departments of Endocrinology, Metabolism and Nuclear Medicine

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Soledad Bell Departments of Endocrinology, Metabolism and Nuclear Medicine

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Silvia Beatriz Christiansen Pathology

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Marcelo Pietrani Radiology

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Mariela Glerean Departments of Endocrinology, Metabolism and Nuclear Medicine

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Monica Loto Departments of Endocrinology, Metabolism and Nuclear Medicine

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Soledad Lovazzano Departments of Endocrinology, Metabolism and Nuclear Medicine

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Antonio Carrizo Neurosurgery, Hospital Italiano, Perón 4190, 1202 Buenos Aires, Argentina

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Pablo Ajler Neurosurgery, Hospital Italiano, Perón 4190, 1202 Buenos Aires, Argentina

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Patricia Fainstein Day Departments of Endocrinology, Metabolism and Nuclear Medicine

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Summary

IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis.

Learning points

  • IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.

  • It is more common in older men, but young women may also present this type of hypophysitis.

  • Although involvement of other organs is frequent, isolated pituitary disease is possible.

  • Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.

  • The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.

  • Glucocorticoids are recommended as first-line therapy.

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Maryam Rahman Department of Neurosurgery

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Ignacio Jusué-Torres Department of Neurosurgery

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Abdulrahman Alkabbani Division of Endocrinology, Department of Medicine

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Roberto Salvatori Division of Endocrinology, Department of Medicine

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Fausto J Rodríguez Department of Pathology, Johns Hopkins University, 600 North Wolfe Street, Phipps 1-111, Baltimore, Maryland 21287, USA

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Alfredo Quinones-Hinojosa Department of Neurosurgery

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Summary

Pituitary adenomas are usually solitary lesions. Rarely, patients may present with two distinct pituitary tumors. We report a case of synchronous secretory pituitary adenomas in a woman who initially presented with elevated prolactin levels. She was initially treated with cabergoline, but, after many years, she began developing symptoms consistent with acromegaly. Imaging revealed two distinct tumors within the pituitary gland. Endocrinological investigation confirmed acromegaly. At the time of surgery, two separate tumors were identified and resected. Pathological analysis demonstrated one tumor as a prolactinoma, and the other tumor as a GH-secreting adenoma. Postoperatively, her GH and IGF1 levels normalized, while the prolactin level remained slightly above normal. This case highlights that GH and prolactin level elevation is not always from co-secretion by the same adenoma.

Learning points

  • Synchronous pituitary adenomas represent <0.5% of pituitary tumors requiring surgery.

  • In the setting of elevated GH and prolactin levels, one cannot assume that they are co-secreted by the same adenoma.

  • A careful study of hormonal workup and pre-operative imaging is necessary for synchronous pituitary adenomas to assure resection of both tumors.

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