Clinical Overview > Hormone > IGF1

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Tzy Harn Chua Department of Endocrinology, Changi General Hospital, Singapore

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Wann Jia Loh Department of Endocrinology, Changi General Hospital, Singapore

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Summary

Severe hyponatremia and osmotic demyelination syndrome (ODS) are opposite ends of a spectrum of emergency disorders related to sodium concentrations. Management of severe hyponatremia is challenging because of the difficulty in balancing the risk of overcorrection leading to ODS as well as under-correction causing cerebral oedema, particularly in a patient with chronic hypocortisolism and hypothyroidism. We report a case of a patient with Noonan syndrome and untreated anterior hypopituitarism who presented with symptomatic hyponatremia and developed transient ODS.

Learning points:

  • Patients with severe anterior hypopituitarism with severe hyponatremia are susceptible to the rapid rise of sodium level with a small amount of fluid and hydrocortisone.

  • These patients with chronic anterior hypopituitarism are at high risk of developing ODS and therefore, care should be taken to avoid a rise of more than 4–6 mmol/L per day.

  • Early recognition and rescue desmopressin and i.v. dextrose 5% fluids to reduce serum sodium concentration may be helpful in treating acute ODS.

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Mauro Boronat Section of Endocrinology and Nutrition, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Research Institute in Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

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Summary

Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.

Learning points:

  • Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.

  • In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.

  • In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

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Diana Catarino Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Cristina Ribeiro Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Leonor Gomes Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Isabel Paiva Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Summary

Pituitary infections, particularly with fungus, are rare disorders that usually occur in immunocompromised patients. Cushing’s syndrome predisposes patients to infectious diseases due to their immunosuppression status. We report the case of a 55-year-old woman, working as a poultry farmer, who developed intense headache, palpebral ptosis, anisocoria, prostration and psychomotor agitation 9 months after initial diabetes mellitus diagnosis. Cranioencephalic CT scan showed a pituitary lesion with bleeding, suggesting pituitary apoplexy. Patient underwent transsphenoidal surgery and the neuropathologic study indicated a corticotroph adenoma with apoplexy and fungal infection. Patient had no preoperative Cushing’s syndrome diagnosis. She was evaluated by a multidisciplinary team who decided not to administer anti-fungal treatment. The reported case shows a rare association between a corticotroph adenoma and a pituitary fungal infection. The possible contributing factors were hypercortisolism, uncontrolled diabetes and professional activity. Transsphenoidal surgery is advocated in these infections; however, anti-fungal therapy is still controversial.

Learning points:

  • Pituitary infections are rare disorders caused by bacterial, viral, fungal and parasitic infections.

  • Pituitary fungal infections usually occur in immunocompromised patients.

  • Cushing’s syndrome, as immunosuppression factor, predisposes patients to infectious diseases, including fungal infections.

  • Diagnosis of pituitary fungal infection is often achieved during histopathological investigation.

  • Treatment with systemic anti-fungal drugs is controversial.

  • Endocrine evaluation is recommended at the time of initial presentation of pituitary manifestations.

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Nicholas J Theis Dunedin School of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

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Toby Calvert Dunedin School of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

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Peter McIntyre Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

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Stephen P Robertson Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

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Benjamin J Wheeler Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

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Summary

Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome.

Learning points:

  • Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels.

  • The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects.

  • Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.

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Misaki Aoshima Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Koji Nagayama Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Kei Takeshita Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Hiroshi Ajima Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Sakurako Orikasa Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Ayana Iwazaki ²Departments of Endocrinology Diabetes and Metabolism, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan

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Hiroaki Takatori Department of Rheumatology, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Yutaka Oki Department of Family and Community Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

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Summary

Patients treated with immunosuppressive drugs, especially methotrexate (MTX), rarely develop lymphoproliferative disorders (LPDs), known as MTX-related LPD (MTX–LPD). The primary site of MTX–LPD is often extranodal. This is the first reported case of MTX–LPD in the pituitary. A 65-year-old woman was admitted to our hospital with symptoms of oculomotor nerve palsy and multiple subcutaneous nodules. She had been treated with MTX for 11 years for rheumatoid arthritis. Computed tomography showed multiple masses in the orbit, sinuses, lung fields, anterior mediastinum, kidney, and subcutaneous tissue. Brain magnetic resonance imaging revealed a sellar mass. She was diagnosed with hypopituitarism and central diabetes insipidus based on endocrine examination. Although pituitary biopsy could not be performed, we concluded that the pituitary lesion was from MTX–LPD, similar to the lesions in the sinuses, anterior mediastinum, and subcutaneous tissue, which showed polymorphic LPD on biopsy. MTX was discontinued, and methylprednisolone was administered to improve the neurologic symptoms. After several weeks, there was marked improvement of all lesions, including the pituitary lesion, but the pituitary function did not improve. When pituitary lesions are caused by MTX–LPD, the possibility of anterior hypopituitarism and central diabetes insipidus needs to be considered. Further studies are needed to investigate the effectiveness of early diagnosis and treatment of MTX–LPD in restoring pituitary dysfunction.

Learning points

  • Pituitary lesions from MTX–LPD may cause hypopituitarism and central diabetes insipidus.

  • Pituitary metastasis of malignant lymphoma and primary pituitary lymphoma, which have the same tissue types with MTX–LPD, have poor prognosis, but the lesions of MTX–LPD can regress only after MTX discontinuation.

  • In cases of pituitary lesions alone, a diagnosis of MTX–LPD may be difficult, unless pituitary biopsy is performed. This possibility should be considered in patients treated with immunosuppressive drugs.

  • Pituitary hypofunction and diabetes insipidus may persist, even after regression of the lesions on imaging due to MTX discontinuation.

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Shinichiro Teramoto Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan

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Yuichi Tange Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan

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Hisato Ishii Department of Neurosurgery, Juntendo University Urayasu Hospital, Chiba, Japan

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Hiromasa Goto Department of Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan

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Ikuko Ogino Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan

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Hajime Arai Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan

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Summary

A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production.

Learning points:

  • Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare.

  • A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components.

  • Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.

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Charlotte Delcourt Departments of Endocrinology and Nutrition, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Halil Yildiz Internal Medicine, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Alessandra Camboni Pathology, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Eric Van den Neste Hematology, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Véronique Roelants Nuclear Medicine, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Alexandra Kozyreff Ophthalmology, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Jean Paul Thissen Departments of Endocrinology and Nutrition, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Dominique Maiter Departments of Endocrinology and Nutrition, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Raluca Maria Furnica Departments of Endocrinology and Nutrition, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Summary

A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of a sarcoidosis–lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment.

Learning points:

  • The possibility of a sarcoidosis–lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies.

  • In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported.

  • An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.

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Hui Yi Ng Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Divya Namboodiri Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Diana Learoyd University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Reserve Road St Leonards, New South Wales, Australia

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Andrew Davidson Department of Neurosurgery, Level 2, Macquarie University, 2 Technology Place Macquarie University, New South Wales, Australia

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Bernard Champion Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Veronica Preda Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Summary

Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up.

Learning points:

  • Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism.

  • Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines.

  • Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.

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Anne Marie Hannon Departments of Endocrinology and Diabetes, Cork University Hospital, Cork, Ireland

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Isolda Frizelle Departments of Endocrinology and Diabetes, Cork University Hospital, Cork, Ireland

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George Kaar Departments of Neurosurgery, Cork University Hospital, Cork, Ireland

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Steven J Hunter Department of Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK

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Mark Sherlock Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland

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Christopher J Thompson Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland

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Domhnall J O’Halloran Departments of Endocrinology and Diabetes, Cork University Hospital, Cork, Ireland

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the Irish Pituitary Database Group
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Summary

Pregnancy in acromegaly is rare and generally safe, but tumour expansion may occur. Managing tumour expansion during pregnancy is complex, due to the potential complications of surgery and side effects of anti-tumoural medication. A 32-year-old woman was diagnosed with acromegaly at 11-week gestation. She had a large macroadenoma invading the suprasellar cistern. She developed bitemporal hemianopia at 20-week gestation. She declined surgery and was commenced on 100 µg subcutaneous octreotide tds, with normalisation of her visual fields after 2 weeks of therapy. She had a further deterioration in her visual fields at 24-week gestation, which responded to an increase in subcutaneous octreotide to 150 µg tds. Her vision remained stable for the remainder of the pregnancy. She was diagnosed with gestational diabetes at 14/40 and was commenced on basal bolus insulin regimen at 22/40 gestation. She otherwise had no obstetric complications. Foetal growth continued along the 50th centile throughout pregnancy. She underwent an elective caesarean section at 34/40, foetal weight was 3.2 kg at birth with an APGAR score of 9. The neonate was examined by an experienced neonatologist and there were no congenital abnormalities identified. She opted not to breastfeed and she is menstruating regularly post-partum. She was commenced on octreotide LAR 40 mg and referred for surgery. At last follow-up, 2 years post-partum, the infant has been developing normally. In conclusion, our case describes a first presentation of acromegaly in pregnancy and rescue of visual field loss with somatostatin analogue therapy.

Learning points:

  • Tumour expansion may occur in acromegaly during pregnancy.

  • Treatment options for tumour expansion in pregnancy include both medical and surgical options.

  • Somatostatin analogues may be a viable medical alternative to surgery in patients with tumour expansion during pregnancy.

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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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