Clinical Overview > Hormone > TSH

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Beverly T Rodrigues Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia

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Zulfiquer Otty Department of Oncology, The Townsville Hospital, Townsville, Queensland, Australia

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Kunwarjit Sangla Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia

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Vasant V Shenoy Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia

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Summary

Autoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.

Learning points

  • AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.

  • It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.

  • Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.

  • Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.

  • Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.

  • Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.

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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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Mahmud Abo Salook Endocrine Institute

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Carlos Benbassat Endocrine Institute
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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Yulia Strenov Pathology Laboratory, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel

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Amit Tirosh Endocrine Institute
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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Summary

A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.

Learning points

  • IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.

  • IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.

  • Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.

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Despoina Manousaki Department of Pediatrics, Endocrine Service, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Cheri Deal Department of Pediatrics, Endocrine Service, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Jean Jacques De Bruycker Department of Pediatrics, Immunology Service, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Philippe Ovetchkine Infectious Disease Division, Department of Pediatrics, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Claude Mercier Surgery Department, Neurosurgery Service, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Nathalie Alos Department of Pediatrics, Endocrine Service, Centre Hospitalier Universitaire Sainte Justine, Université de Montréal, Montreal, Quebec, Canada

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Summary

Cystic sellar lesions are a rare cause of hypopituitarism and extremely rare in the pediatric age group. The differential diagnosis is large and includes both primary pituitary abscesses and cystic components on pre-existing lesions, such as adenoma, craniopharyngioma, Rathke's cleft cyst, leukemia, granulomatous disease and lymphocytic hypophysitis. In the absence of a definitive diagnosis, treatment can be challenging. We report a case of a 15-year-old female, who presented with headaches, altered consciousness and diplopia after a molar extraction, for which she had received oral antibiotics. Broad-spectrum i.v. antibiotics were given for presumed meningitis. Blood cultures failed to identify pathogens. Cerebral magnetic resonance imaging showed a pituitary cystic lesion. Endocrine studies revealed abnormal pituitary function. In the absence of a therapeutic response, the patient underwent a transsphenoidal biopsy of the pituitary gland, which yielded a purulent liquid, but cultures were negative. Histopathology showed lymphocytic infiltrates but no neutrophils, compatible with an inflammation of autoimmune or infectious origin. High-dose glucocorticoid therapy was started and pursued, along with i.v. antibiotics, for 6 weeks, leading to clinical and radiological improvement but with persistence of endocrine deficits. In conclusion, this is a case of secondary panhypopituitarism due to a cystic pituitary lesion, with a differential diagnosis of lymphocytic hypophysitis vs abscess in a context of decapitated meningitis. Combination therapy with antibiotics and glucocorticoids is a legitimate approach in the face of diagnostic uncertainty, given the morbidity, and even mortality, associated with these lesions.

Learning points

  • It is not always easy to differentiate primary cystic sellar lesions (such as a primary infectious pituitary abscess) from cystic components on pre-existing lesions (such as adenoma, craniopharyngioma, Rathke's cleft cyst, leukemia or lymphocytic hypophysitis).

  • Because of the absence of specific symptoms and of immunohistochemical and serum markers, response to glucocorticoids can be the only way to differentiate lymphocytic hypophysitis from pituitary lesions of another origin. In addition, microbiological cultures are negative in 50% of cases of primary infectious sellar abscesses, thus the response to antibiotic treatment is often the key element to this diagnosis.

  • A short course of high-dose glucocorticoids combined with antibiotics is not harmful in cases where there is no diagnostic certainty as to the origin of a cystic sellar mass, given the morbidity and mortality associated with these lesions.

  • This approach may also diminish inflammation of either infectious or autoimmune origin while ensuring that the most likely pathogens are being targeted.

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Lauren J Baker Endocrinology Department, Concord Hospital, Sydney, New South Wales, Australia

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Anthony J Gill Pathology Department, Royal North Shore Hospital, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

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Charles Chan Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
Anatomical Pathology Department, Concord Hospital, Sydney, New South Wales, Australia

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Betty P C Lin Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
Anatomical Pathology Department, Concord Hospital, Sydney, New South Wales, Australia

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Bronwyn A Crawford Endocrinology Department, Concord Hospital, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

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Summary

In 2006, a 58-year-old woman presented with thyrotoxicosis. She had undergone left hemithyroidectomy 14 years before for a benign follicular adenoma. Ultrasound imaging demonstrated bilateral cervical lymphadenopathy with enhanced tracer uptake in the left lateral neck on a Technetium-99m uptake scan. Fine-needle aspiration biopsy of a left lateral neck node was insufficient for a cytological diagnosis; however, thyroglobulin (Tg) washings were strongly positive. The clinical suspicion was of functionally active metastatic thyroid cancer in cervical lymph nodes. A completion thyroidectomy and bilateral cervical lymph node dissection were performed. Histology demonstrated benign multinodularity in the right hemithyroid, with bilateral reactive lymphadenopathy and 24 benign hyperplastic thyroid nodules in the left lateral neck that were classified as parasitic thyroid nodules. As there had been a clinical suspicion of thyroid cancer, and the hyperplastic/parasitic thyroid tissue in the neck was extensive, the patient was given ablative radioactive iodine (3.7 GBq). After 2 years, a diagnostic radioactive iodine scan was clear and the serum Tg was undetectable. The patient has now been followed for 7 years with no evidence of recurrence. Archived tissue from a left lateral neck thyroid nodule has recently been analysed for BRAF V600E mutation, which was negative.

Learning points

  • Thyrotoxicosis due to functional thyroid tissue in the lateral neck is very rare and may be due to metastatic thyroid cancer or benign parasitic thyroid tissue.

  • Parasitic thyroid nodules should be considered as a differential diagnosis of lateral neck thyroid deposits, particularly where there is a history of prior thyroid surgery.

  • Parasitic thyroid nodules may occur as a result of traumatic rupture or implantation from a follicular adenoma at the time of surgery.

  • The use of ablative radioactive iodine may be appropriate, as resection of all parasitic thyroid tissue can prove difficult.

  • BRAF mutational analysis of parasitic thyroid tissue may provide extra reassurance in the exclusion of papillary thyroid carcinoma.

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T Min ST4 Diabetes and Endocrinology, Princess of Wales Hospital, Bridgend CF31 1RQ, UK

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S Benjamin Consultant Diabetes and Endocrinology, Princess of Wales Hospital, Bridgend CF31 1RQ, UK

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L Cozma Consultant Diabetes and Endocrinology, Princess of Wales Hospital, Bridgend CF31 1RQ, UK

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Summary

Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Early recognition and prompt treatment are essential. Atrial fibrillation can occur in up to 40% of patients with thyroid storm. Studies have shown that hyperthyroidism increases the risk of thromboembolic events. There is no consensus with regard to the initiation of anticoagulation for atrial fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated if the risk is low on a CHADS2 score; however, this should be considered in patients with thyroid storm or severe thyrotoxicosis with impending storm irrespective of the CHADS2 risk, as it appears to increase the risk of thromboembolic episodes. Herein, we describe a case of thyroid storm complicated by massive pulmonary embolism.

Learning points

  • Diagnosis of thyroid storm is based on clinical findings. Early recognition and prompt treatment could lead to a favourable outcome.

  • Hypercoagulable state is a recognised complication of thyrotoxicosis.

  • Atrial fibrillation is strongly associated with hyperthyroidism and thyroid storm.

  • Anticoagulation should be considered for patients with severe thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.

  • Patients with severe thyrotoxicosis and clinical evidence of thrombosis should be immediately anticoagulated until hyperthyroidism is under control.

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Gemma Xifra Departments of Diabetes, Endocrinology and Nutrition, Hospital Dr Josep Trueta, Girona, Spain

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Silvia Mauri Departments of Diabetes, Endocrinology and Nutrition, Hospital Dr Josep Trueta, Girona, Spain

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Jordi Gironès Surgery, Hospital Dr Josep Trueta, Girona, Spain

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José Ignacio Rodríguez Hermosa Surgery, Hospital Dr Josep Trueta, Girona, Spain

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Josep Oriola Biochemistry and Molecular Genetics Department, CDB Hospital Clinic, Barcelona, Spain

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Wifredo Ricart Departments of Diabetes, Endocrinology and Nutrition, Hospital Dr Josep Trueta, Girona, Spain

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José Manuel Fernández-Real Departments of Diabetes, Endocrinology and Nutrition, Hospital Dr Josep Trueta, Girona, Spain
CIBERobn, pathophysiology of obesity and nutrition, Spain

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Summary

Background: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy.

Patient findings: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-β (TR β (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 μg/kg per day of l-T4.

Conclusion: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH.

Learning points

  • High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy.

  • The exact role of TR β mutants in thyroid carcinogenesis is still undefined.

  • We report the first case of multiple Hürthle cell adenomas associated with RTH.

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