Successful treatment of Cushing's disease caused by ectopic intracavernous microadenoma.

Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are sometimes difficult to visualize, even with high-quality magnetic resonance imaging, due to their small size and variable location. Sampling the cavernous or inferior petrosal sinus is helpful for confirming the central origin of a tumor, but ectopic corticotroph adenomas in the paraseller region also typically exhibit a high central/peripheral plasma ACTH ratio. We experienced an extremely rare case of Cushing's disease caused by an ACTH-secreting microadenoma located entirely inside the left cavernous sinus attached to the medial wall (ectopic pituitary adenoma) that was not visible by preoperative MRI. In this case, the microadenoma was completely removed and an endocrinologic cure was achieved. This case reveals that in addition to meticulous sectioning of the pituitary gland, bilateral periglandular inspection with visualization of the medial wall of the cavernous sinus and of the diaphragm should always be performed to detect ectopic parasellar microadenomas when no adenoma is visible by preoperative MRI.

The prevalence of polycystic thyroid disease in hypothyroid patients with negative thyroid autoantibodies.

BACKGROUND: We previously reported that multiple thyroid cysts may be a cause of hypothyroidism in patients with a relatively high iodine intake and we termed it polycystic thyroid disease (PCTD). The aim of this study was to investigate the prevalence of PCTD in patients who visited our thyroid center. We hypothesized that patients with PCTD are not rare in a region with a high iodine intake. METHODS: We retrospectively studied the cause of hypothyroidism based on medical histories and ultrasonography in new patients to our hospital from April 2008 to March 2009 whose serum tests for antithyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were negative. Serum thyroid hormones, thyrotropin (TSH), TgAb, and TPOAb were measured in 8243 patients. Patients with four or more thyroid cysts, negative tests for TgAb and TPOAb, no evidence for thyroid diseases other than their thyroid cysts, and no exposure to thyroid-perturbing influences were defined as having PCTD. RESULTS: Three hundred seven patients had overt hypothyroidism (TSH level above 10.0 µU/mL and free thyroxine level below 0.7 ng/dL), of whom 71 patients were both TgAb and TPOAb negative. There were 546 patients with subclinical hypothyroidism (TSH level above 5.0 µU/mL and normal free thyroxine), of whom 193 patients were both TgAb and TPOAb negative. There were 24 patients with overt hypothyroidism and PCTD, accounting for 7.8% (24/307) of all causes of overt hypothyroidism. There were 42 patients with subclinical hypothyroidism and PCTD, accounting for 7.7% (42/543) of all causes of subclinical hypothyroidism. PCTD was more common among elderly people than young people. CONCLUSIONS: PCTD appears to be a minor but not negligible cause of hypothyroidism, at least in iodine-rich regions. PCTD with hypothyroidism may have been misdiagnosed as thyroid antibody-negative Hashimoto's thyroiditis in many reports.

Multiple thyroid cysts may be a cause of hypothyroidism in patients with relatively high iodine intake.

BACKGROUND: Multiple cysts of the thyroid gland have not been recognized as one of the causes of hypothyroidism. Here we present six patients from a region with relatively high iodine intake in whom multiple cysts of the thyroid were associated with hypothyroidism or the development of hypothyroidism. SUMMARY: All patients were women and ranged in age from 49 to 71. Their thyroids were mildly enlarged, tests for thyroid autoantibodies were negative, and multiple cysts were detected in the thyroid by ultrasonography. By dietary questionnaire their iodine intake was estimated to range from 2 to 10 mg of iodine daily. Otherwise, there was no evidence for disorders or factors associated with hypothyroidism. All four patients who agreed to dietary iodine restriction became euthyroid at approximately 1 month after a low-iodine diet (less than 0.5 mg iodine per day) was started. CONCLUSIONS: Although these patients were from a region with high-iodine intake and had a relatively high intake compared with most regions of the world, this amount of iodine intake is not associated with hypothyroidism in otherwise healthy persons. Therefore, we propose that multiple thyroid cysts, which we have termed polycystic goiter, is probably a cause of hypothyroidism in patients with a relatively high iodine intake.

R27X nonsense mutation of the SDHB gene in a patient with sporadic malignant paraganglioma.

It has been estimated that approximately 10% of pheochromocytomas and paragangliomas are part of a hereditary syndrome. Recent studies, however, suggest that the genetic involvement in pheochromocytoma/paraganglioma is actually far more common. Here, we report a case of malignant paraganglioma with no apparent family history. A 59-year-old man was referred to our services because of multiple abdominal masses. Plasma and urine adrenalin and noradrenalin levels were slightly elevated, and plasma dopamine and urine vanillylmandelic acid levels were remarkably elevated. Abdominal and chest computed tomography revealed multiple masses in the para-aortic region and in both lungs. Although (131)I-meta iodobenzylguanidine scintigraphy did not show significant uptake in these tumors, a 6-[(18)F]fluorodeoxyglucose positron emission tomographic scanning study showed multiple areas of uptake corresponding to the tumors. Biopsy of the tumors revealed paraganglioma with chromogranin A-immunopositive cells. Genetic analysis indicated a nonsense mutation at codon 27 of the SDHB gene. As recently described, SDHB mutations may cause extra-adrenal and malignant paragangliomas, such as in the present case.

Lack of ACTH and androgen receptor expression in a giant adrenal myelolipoma associated with 21-hydroxylase deficiency.

Myelolipomas of the adrenal gland are benign, nonfunctioning tumors. Patients with congenital adrenal hyperplasia sometimes develop large and bilateral myelolipomas. Although the precise pathogenesis of myelolipomas remains unclear, prolonged stimulation with high levels of adrenocorticotropic hormone (ACTH) or adrenal androgens are assumed to have a causative role. To clarify the role of ACTH and androgen in the pathogenesis of myelolipoma, we report a case of giant adrenal myelolipoma in a patient with poorly controlled congenital adrenal hyperplasia. A 43-year-old female was diagnosed with congenital adrenal hyperplasia at 6 years of age because of ambiguous genitalia. She had high plasma ACTH and 17-hydroxyprogesterone levels. Abdominal computed tomography showed a huge mass on the left adrenal gland, and an enlarged right adrenal mass. Genetic testing for CYP21A2 was performed and revealed that her genotype was IVS2-13A/C>G/I172N. Adrenalectomy for the left-side tumor was performed. Histological study revealed that the tumor consisted of fat cells and myeloid components, findings compatible with adrenal myelolipoma. Neither ACTH receptors nor androgen receptor was over-expressed in the tumor. Our finding that the tumor did not over-express ACTH or androgen receptor suggests a limited direct role for these hormones in the development of the myelolipoma.

The incidence of gestational hyperthyroidism and postpartum thyroiditis in treated patients with Graves' disease.

Graves' disease (GD) is one of the most common thyroid diseases that cause hyperthyroidism. Gestational transient thyrotoxicosis (GTT) is nonautoimmune hyperthyroidism that occurs in women with a normal pregnancy. Postpartum transient thyroiditis (PTT) is a destructive thyroiditis induced by autoimmune mechanism in the postpartum period. Hyperthyroidism due to GD usually tends to improve during the course of gestation and exacerbate after delivery. When the patient with treated GD presents with thyrotoxicosis in the early pregnancy or in the postpartum period, differential diagnosis of exacerbation of GD with GTT or PTT is important because the latter disorders are fundamentally transient. To evaluate the incidence of GTT and PTT in a GD population, we investigated the thyroid functions, thyrotropin receptor antibodies (TRAb), and human chorionic gonadotropin (hCG) during pregnancy and for 1 year after delivery for 39 pregnancies in 34 women with GD. The incidence of GTT was 26% (10/39) of pregnancies. The peak value of hCG in the GTT group ([23.7 +/- 14.5] x 10(4) IU/mL, n = 9) was significantly higher than that in the non-GTT group ([13.3 +/- 4.7] x 10(4) IU/mL, n = 19). The incidence of PTT was 44% (17/39) of deliveries. The free triiodothyronine (FT(3))/free thyroxine (FT(4)) ratio of the exacerbation group of GD (3.1 +/- 1.0, n = 10) at the time of thyrotoxicosis after delivery was significantly higher than that of the PTT group (2.5 +/- 0.4, n = 16). The peak TRAb value of the exacerbation group of GD (72.5 +/- 121.7 IU/L, n = 10) at the time of thyrotoxicosis after delivery was also significantly higher than that of the PTT group (1.4 +/- 0.8 IU/L, n = 16). In conclusion, the high peak value of hCG is valuable for suspecting GTT, and the high FT(3)/FT(4) ratio is valuable for suspecting recurrence in the patients with GD. In both situations, changes of TRAb were also valuable in differentiating the recurrence of GD from GTT or PTT.