Central hyperthyroidism, characterized by elevated thyroid hormone levels with a nonsuppressed thyroid-stimulating hormone (TSH), presents a diagnostic challenge in distinguishing thyroid hormone resistance (RTH) from a TSH-secreting pituitary adenoma (TSHoma). We report a 56-year-old man with a history of atrial fibrillation, obesity, and obstructive sleep apnea who was referred to our center with a prior diagnosis of RTH made elsewhere. Laboratory testing revealed elevated free T4 (2.2 ng/dL) and total T3 (234 ng/dL) with an inappropriately normal TSH (3.1 μIU/mL). Thyrotropin receptor antibody was negative, and radioactive iodine uptake was diffusely elevated. Pituitary magnetic resonance imaging demonstrated a 6 × 9 × 9 mm pituitary microadenoma, initially raising suspicion for TSHoma. However, a preserved TSH response to thyrotropin-releasing hormone stimulation, partial TSH suppression with high-dose T3, normal TSH α-subunit and sex hormone-binding globulin levels, and a pathogenic thyroid hormone receptor beta gene mutation all supported the diagnosis of RTH. Despite these findings, the patient underwent transsphenoidal pituitary surgery, and histopathology confirmed a plurihormonal PIT-1 lineage adenoma positive for TSH, growth hormone, and prolactin. Postoperatively, the patient recovered well and was discharged home. With postoperative normalization of TSH and free T4, it is conceivable that the pituitary tumor contributed to the TSH elevation, suggesting the possibility of dual pathology-concomitant TSHoma and RTH. This case highlights the diagnostic dilemmas and overlapping features of RTH and TSHoma, emphasizing the need for comprehensive hormonal testing and genetic confirmation to avoid unnecessary surgery.

The coexistence of Graves disease (GD) and a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is a rare and diagnostically challenging condition. In general, GD typically manifests with low TSH because of excess thyroid hormone production; contrastingly, a TSHoma causes secondary hyperthyroidism with normal or elevated TSH levels. This unusual overlap poses diagnostic and therapeutic challenges; therefore, a careful approach is required to distinguish and manage both conditions. We present the case of a 51-year-old woman with symptoms of hyperthyroidism, elevated thyroid hormones, low TSH, and positive anti-TSH receptor antibodies, which were suggestive of GD 10 years prior. After stopping thiamazole and levothyroxine because of the favorable control of thyroid function 6 months prior, the patient presented a syndrome of inappropriate secretion of TSH and magnetic resonance imaging revealed a pituitary macroadenoma; accordingly, she was diagnosed with concurrent GD and a TSHoma. Treatment involved transsphenoidal resection of the TSHoma and antithyroid medication to control GD. This case illustrates the rarity of coexisting GD and TSHoma and the diagnostic and therapeutic complexities of managing dual hyperthyroidism etiologies. Biochemical testing, antibody assessment, and imaging examination are essential for accurate and early diagnosis of the condition.

Thyroid-stimulating hormone (TSH; thyrotropin) adenoma is a rare pituitary tumor that can be missed due to its subtle symptoms. We are reporting a 67-year-old man with history of ventricular fibrillation on amiodarone who presented with acute headache and right third cranial nerve palsy. His computed tomography (CT) scan revealed a 2.2-cm suprasellar mass, consistent with pituitary apoplexy, and he underwent pituitary tumor resection. Preoperational hormonal workup revealed TSH 0.25 mIU/mL (0.25 IU/L) (normal reference range: 0.35-4.94 mIU/mL; 0.35-4.94 IU/L), free thyroxine (T4) 3.17 ng/dL (40.80 pmol/L) (normal reference range: 0.7-1.48 ng/dL; 9.78-19.05 pmol/L), and total triiodothyronine (T3) 91 ng/dL (140 nmol/L) (normal reference range: 58-159 ng/dL; 89-244 nmol/L). Initial differential diagnoses included TSH-producing pituitary adenoma (TSH-oma) and amiodarone-induced thyrotoxicosis. His free T4 declined significantly postoperatively, favoring a TSH-oma diagnosis. The pathology report showed a TSH and growth hormone (GH) cosecreting adenoma. Furthermore, he had a normal thyroid uptake scan, as well as negative thyroid antibodies, making primary thyroid diseases less likely. A high free T4 with normal TSH 3 years ago, prior to the start of amiodarone, suggested a long disease duration. This case demonstrates challenges in diagnosing TSH-oma, especially in patients with normal TSH and concurrent amiodarone use.

TSH-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary tumor, with an increasing incidence over the last decades. Diagnosis is often delayed, exposing patients to a high risk of developing chronic complications of long-standing hyperthyroidism. Although thyroid hormone excess is a recognized cause of secondary osteoporosis, very few studies have investigated skeletal damage in patients with TSHoma, with data limited to bone turnover markers (BTM) and a study on the prevalence of radiological vertebral fractures (VFs) incidentally detected on chest X-ray, whereas data on bone mineral density (BMD) are anecdotal. Bone resorption is increased in TSHoma compared to controls, whereas few case reports described osteoporosis and spine fractures as early complications of TSHoma. A high prevalence of morphometric VFs was described in TSHoma compared to nonfunctioning pituitary adenoma (NFPA). Patients with fracture were older and had higher free thyroxine (fT4) levels than patients without fracture. In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.

Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHβ), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the THRB gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRβ1), suggestive of RTHβ. In vitro and ex vivo studies revealed that the His435Arg mutated TRβ1 (TRβ1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHβ led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios.