Unmasked renal impairment and prolonged hyperkalemia after unilateral adrenalectomy for primary aldosteronism coexisting with primary hyperparathyroidism: report of a case.

We herein report the case of a patient with critical hyperkalemia after unilateral adrenalectomy (ADX) for aldosterone-producing adenomas, which were coexisting with primary hyperparathyroidism. A right adrenal tumor oversecreting mineral corticoid was identified in a 62-year-old female whose kidney function had been impaired due to primary hyperaldosteronism and hyperparathyroidism. The ADX improved her hypertension with normalization of the plasma aldosterone concentration, but without adequately increasing her plasma renin activity. Her eGFR further decreased postoperatively, hyperkalemia appeared and the serum potassium level rose to 6.3 mEq/L at 3 months after ADX. Then, treatment with calcium polystyrene sulfonate jelly was started. Eight months after ADX, a left lower parathyroidectomy was performed, and the serum calcium and intact parathyroid hormone levels decreased to the normal range. The hyperkalemia was difficult to control within 20 months postoperatively without treatment with calcium polystyrene sulfonate jelly or hydrocortisone. This suggests that unmasking the renal impairment and relative hypoaldosteronism after ADX might induce critical hyperkalemia.

Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case.

We report a rare case with pheochromocytoma as the first manifestation of multiple endocrine neoplasia type 2A with RET mutation S891A. Bilateral pheochromocytomas were identified in a 54-year-old woman. Screening for RET revealed a rare S891A mutation located in the intracellular tyrosine kinase domain. This mutation was previously recognized as one of the mutations only in cases manifesting solely medullary thyroid carcinomas (MTCs). Since calcitonin stimulation test indicated positive result, total thyroidectomy was performed 1 year after the bilateral adrenalectomy, and C-cell hyperplasia was diagnosed by histopathological examination. Our report suggests that cases with S891A mutation, akin to those with other RET mutations, require screening for pheochromocytoma. In addition, it is indicated that calcitonin stimulation test should be performed even in the unaffected elder cases with S891A mutation although the mutation is classified as lowest risk group on MTC in guidelines.

A MEN2A family with two asymptomatic carriers affected by unilateral renal agenesis.

Accumulating evidences suggest RET gene's involvement in development of the kidney in mice and humans. Although it is well known that RET mutation causes multiple endocrine neoplasia type 2A (MEN2A), thus far only 3 individuals have been reported to have MEN2A and renal agenesis/dysgenesis. We report a MEN2A family with RET mutation in which two asymptomatic carriers presented with unilateral renal agenesis. A 48-year-old woman underwent total thyroidectomy with regional lymph node dissection in our department for medullary thyroid carcinoma. She had earlier surgical treatment for a left adrenal pheochromocytoma at the age of 45. In the screening for MEN type 2 for her three sons, a CT scan for adrenal pheochromocytoma incidentally found unilateral renal agenesis in two of the sons, one of whom had suffered from Hirschsprung's disease (HSCR). They had contralateral kidneys exhibiting compensatory hypertrophy and normal renal function. Genetic analysis detected C618R RET mutation in the proband and her 3 sons, and no other mutations were found in RET as well as glial cell line-derived neurotrophic factor (GDNF). Our data lend support to the hypothesis that constitutive active RET mutation in MEN type 2 might partially impair RET function and thereby cause loss of function phenotype such as renal agenesis or HSCR.

Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism.

Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RIα expression. PKA activities were determined in several adenomas highly expressing RIα. RIα expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas. In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.

Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients.

PURPOSE: To evaluate the frequency and prognostic importance of neuroendocrine differentiation (NED) in Japanese breast cancer patients. METHODS: We used standard immunohistochemical techniques to examine 50 patients who underwent resection of breast cancer between 1988 and 1993 at the Department of Surgery II, Nagoya University Hospital, for NED, defined as positive reactivity for four markers: neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA). Neuroendocrine differentiation was defined by the presence of at least one marker including CGA, CD57, and synaptophysin, or at least two markers when one was positive for NSE. RESULTS: Neuroendocrine differentiation was found in 13 (26%) of the 50 patients examined. There were no significant differences in the distribution of patients with positive or negative NED in terms of age, menopausal status, tumor size, lymph node metastasis, histological grade, ER, PgR, and HER2. We calculated the cumulative survival rates of patient groups according to NED status, and found no significant difference in overall or disease-free survival between patients with and those without NED. CONCLUSION: Neuroendocrine differentiation was identified in a subset (26%) of Japanese breast cancer patients, but this appeared to have no relationship with established prognostic factors or patient outcome.

Long term parathyroid function following total parathyroidectomy with autotransplantation in adult patients with MEN2A.

While there is no doubt that total thyroidectomy is necessary for medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2A (MEN2A) patients, there is still controversy regarding the management of the parathyroid glands. Although most, but not all, endocrine surgeons leave normal-appearing parathyroid glands in situ during thyroid surgery for MEN2A, we have employed total parathyroidectomy with autotransplantation. Between 1994 and 2006, 12 MEN2A patients underwent therapeutic total or completion thyroidectomy and lymph nodes dissection at least in the central compartment for MTC. Total or completion parathyroidectomy with autotransplantation was performed concurrently with above-mentioned surgery. All patients were over 25 years old, and the median age was 48.5 years. There were 5 males and 7 females from 8 families. The average number of transplanted parathyroid glands was 3. Serum calcium and intact PTH levels have been maintained during the median follow up of 107 months in all patients except for one who of died of advanced MTC one year after surgery. Total parathyroidectomy with autotransplantation at the time of primary surgery for MTC, i.e. total thyroidectomy with bilateral central neck dissection, is a feasible approach for managing the risk of hyperparathyroidism.