Diagnosis and Treatment > Investigation > TRH stimulation
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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:
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Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.
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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.
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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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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:
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Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism.
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Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines.
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Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.
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Department of Pediatrics, Keio Hachioji Clinic, Hchioji, Tokyo, Japan
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Summary
Resistance to thyroid hormone (RTH), which is primarily caused by mutations in the thyroid hormone (TH) receptor beta (THRB) gene, is dominantly inherited syndrome of variable tissue hyposensitivity to TH. We herein describe a case involving a 22-year-old Japanese man with RTH and atrial fibrillation (AF) complaining of palpitation and general fatigue. Electrocardiography results revealed AF. He exhibited elevated TH levels and an inappropriately normal level of thyroid-stimulating hormone (TSH). Despite being negative for anti-TSH receptor antibody, thyroid-stimulating antibody and anti-thyroperoxidase antibody, the patient was positive for anti-thyroglobulin (Tg) antibody. Genetic analysis of the THRB gene identified a missense mutation, F269L, leading to the diagnosis of RTH. Normal sinus rhythm was achieved after 1 week of oral bisoprolol fumarate (5 mg/day) administration. After 3 years on bisoprolol fumarate, the patient had been doing well with normal sinus rhythm, syndrome of inappropriate secretion of TSH (SITSH) and positive titer of anti-Tg antibody.
Learning points:
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Atrial fibrillation can occur in patients with RTH.
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Only a few cases have been reported on the coexistence of RTH and atrial fibrillation.
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No consensus exists regarding the management of atrial fibrillation in patients with RTH.
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Administration of bisoprolol fumarate, a beta-blocker, can ameliorate atrial fibrillation in RTH.
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Division of Endocrinology and Metabolism Division of Endocrinology and Metabolism, International University of Health and Welfare Hospital, Tochigi, Japan
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Summary
Lymphocytic hypophysitis (LyH) has been known to be associated with pregnancy. We herein report the case of a 33-year-old woman who underwent vaginal delivery without massive bleeding at 40 weeks of gestation. Because of the presence of headache and terrible fatigue after childbirth, she visited our hospital. Severe hyponatremia (Na, 118 mEq/L) and visual field abnormality was noted upon examination. MRI revealed pituitary enlargement with a swollen pituitary stalk, albeit at low signal intensity. Basal pituitary hormone levels were all reduced and remained low after exogenous administration of hypothalamic-releasing hormones. She was diagnosed with LyH and was started on prednisolone 60 mg/day. A month later, her pituitary function had gradually improved together with a decrease in pituitary enlargement and recovery of her visual field. The dose of prednisolone was gradually reduced and finally withdrawn 27 months later. After prednisolone withdrawal, her pituitary function remained normal despite the absence of any hormonal replacement. A year later, she became pregnant without medication and delivered a second baby without LyH recurrence. Thereafter, her pituitary function has been normal for more than 5 years. Two valuable observations can be highlighted from the case. First, the patient completely recovered from LyH through prompt prednisolone therapy during its initial phase and had almost normal pituitary function. Second, after recovery from LyH, she was able to undergo spontaneous pregnancy and deliver a baby. We believe that reporting incidences of spontaneous pregnancy after complete normalization of pituitary function in patients with LyH is of great significance.
Learning points:
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Females are more affected by LyH than males given its strong association with pregnancy.
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LyH possesses characteristic findings on pituitary MRI.
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Glucocorticoid therapy for LyH has been recommended as an effective treatment.
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A history of previous pregnancies does not increase the risk of developing AH in subsequent pregnancies.
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Early induction of high-dose prednisolone was therapeutically effective in treating LyH.
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Summary
A 76-year-old man had a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism. Based on various findings including the swelling of the pituitary gland, increase of serum IgG4 level and abundant IgG4-positive plasma cell infiltration in immunostaining of the pituitary gland, we diagnosed this subject as IgG4-related hypophysitis. In general, a high-dose glucocorticoid treatment is effective for IgG4-related disease. His clinical symptom, laboratory data and adrenal insufficiency were almost improved without any therapy. The serum IgG4 level was decreased and pituitary size was normalized with hydrocortisone as physiological replacement. This case report provides the possibility that IgG4 level is decreased spontaneously or with physiological dose of glucocorticoid therapy.
Learning points:
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We performed the pituitary gland biopsy and histochemical examination glucocorticoid therapy in a subject with IgG4-related hypophysitis.
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This case report provides the possibility that IgG4 level is decreased spontaneously or with a physiological dose of glucocorticoid therapy. We reported the clinical course of IgG4-related hypophysitis without a high-dose glucocorticoid treatment, although there were a few reports about the retrospective examination.
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Although the patient had still higher IgG4 level compared to normal range, his clinical symptom disappeared and his laboratory data were improved.
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We should keep in mind the possibility of IgG4-related hypophysitis when we examine one of the uncertain causes of a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism.
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Summary
TSH-secreting pituitary adenomas are rare and the optimal investigation and management is uncertain. We describe a case of a 43 year-old woman with a TSH-secreting pituitary adenoma, highlighting diagnostic testing and our use, pre-operatively of somatostatin analogue therapy, which induced biochemical euthyroidism and a reduction in tumour size.
Learning points
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The differential diagnosis of the syndrome of inappropriate TSH secretion is non-thyroidal illness, medications, assay interference due to heterophilic antibodies, thyroid hormone resistance and TSH-secreting pituitary adenoma.
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TRH stimulation test and triiodothyronine suppression test assist in differentiating thyroid hormone resistance and TSH-secreting pituitary adenoma.
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Somatostatin analogue therapy can induce biochemical euthyroidism and reduce tumour size.