Dynamic changes of central thyroid functions in the management of Cushing's syndrome

ABSTRACT Objective The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. Materials and methods We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. Results The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Conclusion Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

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.