A Case of Primary Aldosteronism Turned Out to Be Adrenocortical Carcinoma With Disorganized Steroidogenesis.

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis, which essentially needs an early diagnosis because surgery is the only hope of a cure. On the other hand, primary aldosteronism (PA) is an overproduction of aldosterone from the adrenal glands and is known as one of the most common causes of secondary hypertension and hypokalemia. It is mostly a benign disease. ACC accompanied by PA is extremely rare, which can result in delayed diagnosis and clinical pitfalls. A 56-year-old woman was diagnosed with PA. Mild, symptomatic PA was clinically diagnosed as a right-sided aldosterone-producing adenoma (APA) with adrenal tumor using adrenal vein sampling (AVS). The tumor imaging findings showed abnormalities on computed tomography (CT) in terms of size and attenuation value compared with typical benign adenomas. Twelve months later, the tumor was confirmed to be an ACC with cortisol hypersecretion. The resected ACC specimen did not clearly show positive findings for CYP11B1 or CYP11B2, and disorganized steroid production was suspected. However, the prevalence and clinical characteristics of adrenocortical carcinomas with disorganized steroid production remain unclear. Steroidogenic enzyme immunostaining analysis is important not only for the diagnosis of adrenal adenoma but also for a better understanding of the clinical course of hormone-producing ACC.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells.

The mechanism whereby 17ß-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10-9 to 1 × 10-7 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of the insulin promoter region revealed that nucleotide positions - 238 to - 144 (relative to the transcriptional start site) were needed for ER repression of the rat insulin II gene. PDX1- and BETA2-binding sites were required for the repression, but an estrogen response element-like sequence or an AP1 site in the promoter was not involved. In conclusion, we found that estrogen repressed insulin mRNA expression in a beta cell line. In addition, the ER suppressed insulin gene transcription in a ligand-independent matter. These observations suggest ER may regulate insulin transcription by indirect genomic signaling.

Loss of µ-crystallin causes PPARγ activation and obesity in high-fat diet-fed mice.

The thyroid hormone-binding protein µ-crystallin (CRYM) mediates thyroid hormone action by sequestering triiodothyronine in the cytoplasm and regulating the intracellular concentration of thyroid hormone. As thyroid hormone action is closely associated with glycolipid metabolism, it has been proposed that CRYM may contribute to this process by reserving or releasing triiodothyronine in the cytoplasm. We aimed to clarify the relationship between CRYM and glycolipid metabolism by comparing wild-type and CRYM knockout mice fed a high-fat diet. Each group was provided a high-fat diet for 10 weeks, and then their body weight and fasting blood glucose levels were measured. Although no difference in body weight was observed between the two groups with normal diet, the treatment with a high-fat diet was found to induce obesity in the knockout mice. The knockout group displayed increased dietary intake, white adipose tissue, fat cell hypertrophy, and hyperglycemia in the intraperitoneal glucose tolerance test. In CRYM knockout mice, liver fat deposits were more pronounced than in the control group. Enhanced levels of PPARγ, which is known to cause fatty liver, and ACC1, which is a target gene for thyroid hormone and is involved in the fat synthesis, were also detected in the livers of CRYM knockout mice. These observations suggest that CRYM deficiency leads to obesity and lipogenesis, possibly in part through increasing the food intake of mice fed a high-fat diet.

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.

A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing's disease and a left adrenal tumor.

A 67-year-old female with hypertension and impaired glucose tolerance was admitted to our hospital because of a typical acromegalic appearance, including large, thickened bulky hands and feet, and a large prominent forehead and tongue. She did not have a Cushingoid appearance, such as a moon-face, buffalo hump, purple striae or central obesity. The laboratory data revealed a serum GH level of 4.6 ng/mL and serum insulin-like growth factor-1 level of 811 ng/mL. The oral glucose tolerance test showed no suppression of the GH values. An endocrine examination showed a lack of circadian rhythmicity of ACTH and cortisol. Cortisol was not suppressed by a low dose of dexamethasone during the suppression test, but was suppressed by a high dose of dexamethasone. A radiological study revealed two isolated adenomas in the pituitary and a left adrenal tumor. These findings strongly suggested a diagnosis of acromegaly with subclinical Cushing's disease and a left adrenal incidentaloma. Transsphenoidal surgery was performed. Hematoxylin and eosin staining showed that the left and right pituitary adenomas were composed of basophilic and acidophilic cells, respectively. Immunohistochemical staining showed the left adenoma to be positive for ACTH and negative for GH. In contrast, the right adenoma was GH-positive and ACTH-negative. This is a rare case of independent double pituitary adenomas with distinct hormonal features. We also provide a review of the previously reported cases of double pituitary adenomas and discuss the etiology of these tumors.