Diagnosis and Treatment > Signs and Symptoms
Search for other papers by Hui Yi Ng in
Google Scholar
PubMed
Search for other papers by Divya Namboodiri in
Google Scholar
PubMed
Search for other papers by Diana Learoyd in
Google Scholar
PubMed
Search for other papers by Andrew Davidson in
Google Scholar
PubMed
Search for other papers by Bernard Champion in
Google Scholar
PubMed
Search for other papers by Veronica Preda in
Google Scholar
PubMed
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.
Search for other papers by Guadalupe Vargas in
Google Scholar
PubMed
Search for other papers by Lourdes-Josefina Balcazar-Hernandez in
Google Scholar
PubMed
Search for other papers by Virgilio Melgar in
Google Scholar
PubMed
Search for other papers by Roser-Montserrat Magriña-Mercado in
Google Scholar
PubMed
Search for other papers by Baldomero Gonzalez in
Google Scholar
PubMed
Search for other papers by Javier Baquera in
Google Scholar
PubMed
Neurological Center
Search for other papers by Moisés Mercado in
Google Scholar
PubMed
A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.
Learning points:
-
Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.
-
Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.
-
Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.
Search for other papers by Arshiya Tabasum in
Google Scholar
PubMed
Search for other papers by Ishrat Khan in
Google Scholar
PubMed
Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
Search for other papers by Peter Taylor in
Google Scholar
PubMed
Search for other papers by Gautam Das in
Google Scholar
PubMed
Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
Search for other papers by Onyebuchi E Okosieme in
Google Scholar
PubMed
Summary
TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.
Learning points
-
Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies.
-
Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.
-
Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.
Search for other papers by Annika Sjoeholm in
Google Scholar
PubMed
Search for other papers by Cassandra Li in
Google Scholar
PubMed
Search for other papers by Chaey Leem in
Google Scholar
PubMed
Search for other papers by Aiden Lee in
Google Scholar
PubMed
Search for other papers by Maria P Stack in
Google Scholar
PubMed
Search for other papers by Paul L Hofman in
Google Scholar
PubMed
Paediatric Endocrinology, Southern District Health Board, Dunedin, New Zealand
Search for other papers by Benjamin J Wheeler in
Google Scholar
PubMed
Summary
Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.
Learning points
-
Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.
-
The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.
-
As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.
-
Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.
