Gonadotropin-secreting and thyrotropin-secreting pituitary adenomas: A single-center experience

ABSTRACT Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India. Materials and methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical (inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas. Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas). Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger and had low surgical cure rates.

Thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1: one case report and literature review / 中华内分泌代谢杂志

Objective@#To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder.@*Methods@#The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard.@*Results@#One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported.@*Conclusion@#Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare.

Macrodenoma hipofisario productor de TSH y GH tratado con dosis mensuales del análogo de somatostatina lanreotide. Caso clínico / Pituitary macroadenoma cosecreting thyrotropin and somatotropin treated with monthly doses of the somatostatin analog lanreotide. A case report

Los tirotropinomas son una causa rara de hipertiroidismo, con una prevalencia de un caso por millón de habitantes. Representanmenos del 2% de todos los adenomas pituitarios. Se caracterizan por la secreción autónoma de tirotrofina (TSH) y la refractariedada la retroalimentación negativa de las hormonas tiroideas. Los adenomas mixtos se diferencian por la hipersecreción concomitantede otra hormona de la hipófisis anterior, y se encuentran hasta un 25% de los pacientes, siendo el 15% productoresde somatotrofina (GH).Debido a su infrecuencia, presentamos el caso de una mujer de 62 años, con antecedente de enfermedad de Graves diagnosticadaa los 28 años de edad, tratada con dos dosis de iodo radioactivo. Es derivada a nuestro servicio a la edad de 62 años conel siguiente laboratorio: TSH 38 µUI/ml (0,3-4,2), T4 12.8 µg/ml (4,5-12,5) e IGF-1 445 ng/ml (81-230) y una resonanciamagnética nuclear (RMI) que informaba un macroadenoma hipofisario invasivo. Tras la actualización de los estudios y laconfirmación diagnóstica se inició tratamiento médico con lanreotide intramuscular, 120 mg cada 28 días, obteniendo buenarespuesta bioquímica.

Thyrotropin secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism with a prevalence of about one case permillion. They account for less than 2% of all pituitary adenomas. TSH secretion is autonomous and refractory to the negative feedbackof thyroid hormones. Mixed adenomas are characterized by concomitant hypersecretion of other anterior pituitary hormones, and arefound in about 25% of patients; approximately 15% secrete somatotropin (GH).Because of their rarity, we report the case of a 62 year old women with a history of Graves’ disease diagnosed at 28 years of age,treated with two doses of I-131, and referred to our service with the following laboratory: TSH 38 µIU/ml (0.3-4.2), T4 12.8 µg/ml(4.5-12.5) and IGF-1 445 ng/ml (81-230). RMI showed an invasive pituitary macroadenoma. After updating and confirming thecomplementary studies, medical treatment was started with the somatostatin analog lanreotide, 120 mg i.m. every 28 days; there wasgood biochemical response.

Adenoma hipofisario productor de TSH (tirotropinoma): presentación de cinco casos / TSH Secreting Pituitary Adenoma (Thyrotropinoma): Five Case Reports

El tirotropinoma es el adenoma hipofisario menos frecuente (< 2 %). Debido a su infrecuencia, describimos 5 casos. Caso 1: Varón de 23 años, presentó fibrilación auricular aguda. El perfil tiroideo mostró: TSH: 4,2 uUI/ml (0,3-4), T4: 14,8 ug/dl (4,5-12,5), T4L: 2,2 ng/dl (0,8-1,9),T3: 170 ng/dl (80-180), T3L: 7,8 pg/ml (1,8-4,6) y test de TRH-TSH plano. La resonancia nuclear magnética (RNM) de cerebro reveló un macroadenoma. Se inició tratamiento con metimazol sin lograr respuesta apropiada. Luego comenzó tratamiento con octreótido-Lar logrando el eutiroidismo. Fue intervenido por vía transesfenoidal (TE), confirmándose por inmunohistoquímica (IHQ) adenoma (+) para TSH. A los 7 días luego de la cirugía la TSH se constató suprimida. Cinco años después se encuentra en remisión. Caso 2: Mujer de 41 años, consultó por hipertiroidismo bioquímico e hipertensión arterial (HTA). La evaluación hormonal mostró: TSH: 3,21 uUI/ml (0,4-4), T4: 16,9 ug/dl (4,5-10,9), T4L: 2,2 ng/dl (0,8-1,5), T3: 245 ng/dl (60-180) y test de TRH-TSH plano. La RNM evidenció un microadenoma de 2 mm. La terapia con cabergolina no modificó las hormonas tiroideas. El tumor mostró crecimiento progresivo (10,8 mm a los 2 años). Se operó por vía TE y el tumor fue (+) en la IHQ para TSH y GH. Luego de la cirugía presentó TSH suprimida por 15 días. Actualmente lleva un año y medio libre de enfermedad. Caso 3: Hombre de 53 años consultó por disminución de la libido, impotencia sexual y aumento de peso. El laboratorio reveló: TSH: 9,1 uUI/ml, T4L: 1,79 ng/dl (0,9-1,8), T3: 164 ng/dl (40-181). En la RNM se halló un macroadenoma. Se realizó cirugía TE, el adenoma fue (+) para TSH y GH en la IHQ. Evolucionó con hipotiroidismo primario. Caso 4: Mujer de 36 años consultó por hipertiroidismo. El perfil tiroideo reveló: TSH: 3,76 uUI/ml (0,4-4), T4: 13,2 ug/dl (4-12), T4L: 2,3 ng/dl (0,9-1,7), T3: 247 ng/dl (70-200) y test TRH-TSH plano. La RNM evidenció un adenoma de 10 mm. Se intervino ...

Thyrotropinomas are the less frequent adenomas (< 2 %). Because of their infrequency, we report 5 cases. Case 1: 23-year-old man, with sudden atrial fibrillation. The hormonal profile showed: TSH: 4.2 uIU/ml (0.3-4), T4: 14.8 ug/dl (4.5-12.5), FT4: 2.2 ng/dl (0.8-1.9), T3: 170 ng/dl (80-180), FT3: 7.8 pg/ml (1.8-4.6) and flat TRH test. MRI revealed a macroadenoma. Therapy with metimazol was initiated, without response. Subsequently, treatment with octreotide-Lar was started and euthyroidism was reached. He underwent transsphenoidal surgery. Immunohistochemistry was positive for TSH. One week after surgery, TSH was suppressed. He has been free of disease for the last 5 years. Case 2: 41-year-old woman with biochemical hyperthyroidism and hypertension. Labs showed: TSH: 3.21 uIU/ml (0.4-4), T4: 16.9 ug/dl (4.5-10.9), FT4: 2.2 ng/dl (0.8-1.5), T3: 245 ng/dl (60-180) and flat TRH test. On MRI a microadenoma of 2 mm was diagnosed. Therapy with cabergoline did not normalize thyroid hormones. The tumor grew to 10.8 mm after 2 years. Transsphenoidal surgery was performed. Immunohistochemical staining was positive for TSH and GH. She evolved with suppressed TSH for 15 days. She has been free of disease for the last 18 months. Case 3: 53-year-old man, with loss of libido, sexual impotence and weight gain. Laboratory tests revealed: TSH: 9.1 uIU/ml, FT4: 1.79 ng/dl (0.9-1.8), T3: 164 ng/dl (40-181). MRI showed a macroadenoma. Trans­sphenoidal surgery was performed, the adenoma was positive for TSH and GH. The patient evolved with primary hypothyroidism. Case 4: 36-year-old woman who presented with hyperthyroidism. The thyroid profile revealed: TSH: 3.76 uIU/ml (0.4-4), T4: 13.2 ug/dl (4-12), FT4: 2.3 ng/dl (0.9-1.7), T3: 247 ng/dl (70-200) and TRH test was flat. MRI showed an adenoma of 10 mm. She underwent transsphenoidal surgery. Immunohistochemical staining was positive for TSH and GH. She evolved with suppressed TSH for 15 days. She has been free of disease for the last 8 years. Case 5: 49-year-old man, with decreased libido and occasional headaches. The hormonal evaluation revealed: TSH: 14.4 uIU/ml (0.3-4.9), T4: 14.8 ug/dl (4.5-12), T4L: 4.1 ng/dl (0.8-1.5). On MRI an invasive macroadenoma was found. Therapy with octreotide-Lar was started and he was lost to follow-up. Conclusions: We report these cases because of their low prevalence. We emphasize that clinical presentation was variable. We can speculate on the secretion of a less biologically active TSH for cases with no symptoms of hyperthyroidism. Five out of five (5/5) showed non-suppressed TSH, 3/5 presented a macrodenoma at ini­tial diagnosis, 3/5 showed TSH suppression one week after surgery, which might be considered as a criteria of cure. Four out of four patients operated on were cured. Rev Argent Endocrinol Metab 51:141-150, 2014 No financial conflicts of interest exist.

Inappropriate Secretion of TSH Syndrome / Síndrome de secreción Inapropiada de TSH

The syndrome of inappropriate secretion of TSH was the term originally coined to indicate two forms of central hyperthyroidism, i.e. thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) and resistance to thyroid hormone action (RTH). Both forms are characterized by high levels of free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of measurable TSH concentrations, a biochemical picture which is in contrast to primary hyperthyroidism where TSH levels are always undetectable. Patients with TSHoma are clinically hyperthyroid, while RTH patients are generally euthyroid (so-called generalized RTH). However, in a minority of RTH thyrotoxic patients, features have been described with such individuals being deemed to have predominant central or pituitary resistance. Although incidence of inappropriate secretion of TSH is generally low, it is essential to rule out the likely causes of discordance in the TSH/T4 (thyroxine) relationship. The distinction between TSHoma and PRTH can be difficult since both conditions do not present significant differences in age, sex, gender or concentrations of TSH, FT4 and FT3. The failure to recognize them as different entities may have deleterious consequences, such as thyroid ablation in patients with central hyperthyroidism, or unnecessary pituitary surgery in those with PRTH. The objective of this review is to properly characterize them with a history of an affected first-degree relative, biochemical dynamic tests, pituitary imaging and genetic testing, according to what has been reported in international literature, and to analyze biochemical difficulties in choosing the best biochemical tools for that purpose, taking into account that no individual biochemical test can validate the differential diagnosis that must be based on a combination of: serum SUα, SUα/TSH ratio, TSH response to TRH, TSH response to suppression with LT3, and genetic analysis.

Síndrome de secreción inapropiada de TSH fue el término acuñado originalmente para describir dos formas de hipertiroidismo central, los adenomas hipofisarios secretantes de tirotrofina (TSH) (TSHoma) y la resistencia a las hormonas tiroideas (RHT). Ambas condiciones están caracterizadas por niveles elevados de tiroxina libre (T4L) y triiodotironina libre (T3L), en presencia de concentraciones medibles de TSH, escenario bioquímico que contrasta con el hipertiroidismo primario donde los niveles de TSH son siempre indetectables. Los pacientes con TSHoma son clínicamente hipertiroideos, mientras que los pacientes con RHT son generalmente eutiroideos (RHT generalizada). Sin embargo, en una minoría de pacientes tirotóxicos con RHT se han descripto signos y síntomas que los caracterizan como portadores de RHT predominantemente central o hipofisaria (RH). Aunque la incidencia del síndrome de secreción inapropiada de TSH es generalmente baja, es fundamental descartar la discordancia de la relación TSH/T4 (tiroxina). La distinción entre TSHoma y RH puede ser dificultosa ya que ambas condiciones no presentan diferencias significativas en cuanto a edad, sexo, género ni concentraciones de TSH, T4L y T3L. La falla en reconocerlas como diferentes puede tener consecuencias deletéreas, como la ablación tiroidea en pacientes con hipertiroidismo central, o cirugía hipofisaria innecesaria en aquellos con RH. El objetivo de esta revisión es caracterizarlas apropiadamente con la historia de un familiar de primer grado afectado, pruebas bioquímicas dinámicas, imágenes hipofisarias y pruebas genéticas, acorde a lo reportado en la literatura internacional, y al mismo tiempo, analizar las dificultades bioquímicas al elegir la mejor herramienta para tal fin; teniendo en cuenta que ninguna por sí sola puede avalar el diagnóstico diferencial que debe basarse en una combinación de pruebas: concentración sérica de SUα y relación SUα/TSH, tipo de respuesta de TSH al TRH, respuesta de TSH a la supresión con LT3 y análisis genético.

Clinical characteristics and diagnostic analysis of thyrotropinoma / 中华内分泌代谢杂志

Objective To analyze clinical charaCteristics and diagnostic experience on thyrotropinoma (TSHoma).Methods Clinical characteristics,laboratory findings,diagnostic experience,and surgical outcome were summarized from 16 cases of TSHoma in our hospital from January 2006 to September 2011.Results ( 1 )Among 16 cases ( 9 male,7 female ) aged ( 51.63 ± 13.23 ) years,14 ( 87.5 ％ ) cases presented with hyperthyroidism and 2 were diagnosed by physical examination. None of them had exophthalmos, acropachy, or pre-tibial myxedema.( 2 ) Serum FT4 and FT3 levels were all above normal range with serum TSH ( 4.37 ± 2.77 ) μIU/ml.There were 25％ (4/16) cases with positive serum thyroglobulin antibody and/or thyroid peroxidase antibody,none with positive TSH receptor antibody.TRH stimulating test was performed in 9 cases,3 were with positive response ( peak TSH level increased by 5.45-9.20 μIU/ml compared with baseline),and 6 without response (peak TSH level increased by -0.01-3.15 μIU/ml compared with baseline).TSH was suppressed to 27.15％ (5.19％-99.15 ％ ) of the baseline in 11 cases in which somatostatin suppression test was carried out.Prolactin and insulin-like growth factor-Ⅰ levels were increased in 2 cases.MRI performed in 15 patients showed 10 cases of microadenomas and 5 cases of pituitary adenoma.A mass in nasal cavity was found in one case,where no mass was found in the pituitary.( 3 )Surgery was made in 11 cases ( 9 patients underwent transsphenoidal operation,one craniotomy,and one underwent operation via endoscopic nasal septum ). All patients (11/11) were proved to yield pituitary adenoma pathologically.Conclusion Thyrotropinoma should be considered in hyperthyroidism with unsuppressed TSH level,and dynamic tests facilitated early diagnosis.Ectopic thyrotropinoma shoull be considered when normal pituitary morphology was shown by MRI.