A 59 year-old housewife was admitted to the emergency service with a sudden onset of chest pain and nausea.
Initially she was treated as an acute myocardial infarction, but conventional treatments were not effective, and she was sent to our hospital for further evaluation. Her ECG showed several abnormal findings including T-wave inversion, atrial flutter, QT-time prolongation, ST-segment depression or elevation, and frequent ventricular ectopic beats. The echocardiogram, ²⁰¹thalium scintigram and coronary angiography were almost normal. Both urinary and plasma levels of catecholamines were remarkably increased, and the plasma epinephrine was extremely high during attacks. Abdominal echotomography and CT-scanning showed a large left adrenal tumor. The ¹³¹ MIBG scintiscan revealed a high accumulation in this tumor. Then the patient was diagnosed as having pheochromocytoma and catecholamine-induced myocarditis.
The administration of phentolamine (10mg) normalized the inversion of T-wave and the high blood pressure. But when propranolol (2mg) was administrated in addition to phentolamine, the ECG showed a biphasic low T-wave change. According to these phenomena, we supposed that the α-adrenergic receptor was involved in the development of the ST-T changes of the ECG, and the α-adrenergic receptor of this patient might be sensitive under excessive catecholamines, according to the inhibition of the β-receptor by propranolol.

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Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented.
A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholestrelemia and hypernatremia. Erythocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows : Free T3 7.6pg/ml, Free T4 3.3ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with ^99m Tc revealed no uptake in the thyroid area. These findings led us to the diagnosis of “painless autoimmune thyroiditis”. She had become hypothyroid without any medication. At that time radioactive ^99m Tc and ¹²³I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was comfirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988).
This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of “painless thyroiditis” in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.

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The germinal vesicle (GV) of follicle-enclosed oocytes in mice remains arrested at the dictyate state of meiosis. Upon releasing the oocytes from the follicles, the meiotic process resumes, leading to dissolution of the GV, suggesting that factors in the follicular constituents sustain the meiotic arrest of oocytes. Vasoactive intestinal peptide (VIP) was demonstrated in the ovary and found to have a wide range of biological effects. In this study, the possibility of VIP to be a factor which induces meiosis-arrest of oocytes was evaluated. Porcine VIP inhibited resumption of meiosis of cumulus-enclosed mouse oocytes in vitro.Germinal vesicle breakdown (GVBD) was prevented in more than 50% of the oocytes treated by VIP at a concentration of 30μ4. The inhibiting effect of VIP was dose-dependent and reversible. Spontaneous resumption of meiosis of isolated oocytes in vitro was reported to be inhibited by dibutyryl cAMP (dbcAMP) added to the medium, indicating that meiotic arrest can be sustained by maintaining intraoocyte cAMP above a critical level. It was further reported that follicular fluid coutains substances that maintain meiotic arrest in association with exogenous dbcAMP. In the present study, the blocking activity of dbcAMP for the spontaneous resumption of meiosis was not potentiated by the addition of VIP in the medium. The present results suggest that VIP may play a role in the regulation of resumption of oocyte meiosis, and that VIP is not a substance which maintains meiotic arrest in association with cAMP.

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In order to evaluate the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-AD), which has been reported to be an amplifier of mineralocorticoid, the changes in several humoral factors were observed in 19-OH-AD treated rats as compared to those in DOCA hypertensive rats.
Twenty-five male Wistar rats were castrated at 11 weeks of age, and the experiments were begun at 12 weeks of age. The rats were divided into 3 groups. The control group (n = 8) was given an s.c. injection of 0.2 ml of sesame oil. The 19-OH-AD group (n = 10) was injected s.c. with 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group (n = 8) was injected s.c. with 10 mg of DOCA dissolved in 0.2 ml of sesame oil three time weekly. The urine was collected for a period of 24 hours, and the urine volume, and urinary excretions of electrolytes, prostaglandin E₂ (PGE₂), kinin and catecholamine were measured before and after the start of the experiment. The systolic blood pressure (S.B.P.) was measured by the tail-cuff method.
The S.B.P. values before and at 9 weeks after the start of the experiments were 136.7 ± 3.8 and 156.0 ± 2.6 mmHg in the 19-OH-AD group, and 140.6 ± 5.6 and 179.3 ± 5.5 mmHg in the DOCA group, respectively. Body weight, which was elevated in both groups, was higher in the 19-OH-AD group than in the DOCA group. Water intake and urine volume were significantly (p<0.001) increased only in the DOCA group. The urinary Na/K ratio was significantly (p<0.001) elevated in the DOCA group as compared to that in the other two groups. However, there was no significant difference in urinary Na/K ratio between the control and 19-OH-AD groups. The urinary PGE₂ and kinin excretions were significantly (p<0.01) increased in the DOCA group but did not change appreciably in the 19-OH-AD group. The urinary catecholamine excretion was significantly increased in the DOCA group. However, there were no differences in the catecholamine excretion between the control and 19-OH-AD groups.
These experimental results suggest that the mechanism of the hypertensinogenic action of 19-OH-AD differs from that of mineralocorticoid dependent hypertension, such as DOCA hypertension, since the urinary Na/K ratio, and the urinary excretions of PGE₂, kinin and catecholamine did not change appreciably during the elevation of blood pressure induced by the 19-OH-AD administration.

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Altered sodium intake is known to cause a greater change in plasma 18-hydroxycorticosterone (18-OHB) level than in plasma aldosterone level, resulting in an increase of plasma 18-OHB/aldosterone ratio in sodium-depleted man and rats. To evaluate the role of endogenous angiotensin II in the high plasma 18-OHB/aldosterone ratio in sodium-depleted rats, we examined the effect of the angiotensin I converting enzyme inhibitor SQ 14225 on plasma 18-OHB and aldosterone in sodium-depleted (SD) and sodium-repleted (SR) conscious rats.
Plasma renin activity (PRA) and plasma angiotensin II were higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused an increase in PRA and a decrease in plasma angiotensin II, whereas these changes were more prominent in the SD rats than in the SR rats.
Plasma 18-OHB and aldosterone levels were higher in the SD rats than in the SR rats. The plasma 18-OHB/aldosterone ratio was also higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused decreases in plasma 18-OHB and aldosterone levels in both the SR and SD rats, whereas the SQ 14225-induced decreases in plasma 18-OHB and aldosterone levels were more prominent in the SD rats than in the SR rats. Thus, the ingestion of SQ 14225 induced a decrease in the plasma 18-OHB/aldosterone ratio in both the SR and SD rats. The decrease in plasma 18-OHB/aldosterone ratio was more prominent in the SD rats than in the SR rats. On the other hand, the ingestion of SQ 14225 did not affect plasma corticosterone in the SD and the SR rats.
These results suggest that sodium depletion modulates the step of the first 18-hydroxylation in aldosterone biosynthesis, through an increase in endogenous angiotensin II.

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A study of the pathophysiology in our previously reported case of gLucocorticoidresponsive hyperaldosteronism (Case E.H., 17 yrs old, female; JCEM, 28 : 1807, 1968), who were undergone a long-term successful treatment for 21 yrs of daily 0.5 mg dexamethasone (Dex), suggested again that the patient had 17 α -hydroxylase deficiency (17-OH-D) in the adrenal with minimum enzyme deficiency in the ovary. When Case E.H. was injected with zinc-ACTH for 3 days with daily 0.5 mg Dex administration, plasma levels of 17-deoxy-steroids were moderately or dramatically increased, but those of 17 a -hydroxy-steroids (17-OH-steroids) responded poorly or not at all. Plasma level of estraidol and urine estrogens were found to be normal in repeated measurements. Plasma basal levels of LH and FSH were normal, and their responses to LH-RH were high normal or slightly exaggerated. Her menstruation was almost regular, and the basal body temperature was at least biphasic with daily 0.5 mg Dex treatment. However, she did not become pregnant during the 17 yrs of her married life.
Then, we surveyed 31 Japanese cases of 17-OH-D with suppressed plasma renin activity (PRA) to ascertain whether similar patients to our case, 17-OH-D with suppressed PRA and with hyperaldosteronism, has been reported or not. In this survey work, 9 such cases were found to have high plasma aldosterone (Ald) concentration (PAC) (group I). The other 21 cases had normal or low normal PAC, and the one remaining case had low urine Ald (group II).
17-Deoxy-steroids such as corticosterone, 11-deoxycorticosterone and progesterone, which were elevated in this disorder, were added to control plasma, and PAC was measured with Dainabot' s “ALDOSTERONE-RIAKIT^®” used for the measurement of PAC in all group I patients. With the total of large amounts of 600 ng of these 17-deoxysteroids (200 ng for each), however, the incremental PAC value was much less than the lowest PAC value in patients of group I. PAC of one group I patient was measured directly by “ALDOSTERONE-RIAKIT^®” “and also by RIA after extraction and purification procedure using LH-20 column chromatography. The PAC values obtained by both methods were high and the same (285 pg/ml). In 5 out of 22 group II patients, PAC was also measured with the same RIA kit” ALDOSTERONE-RIAKIT^® mentioned above, and yet it was low or low normal.
Plasma cortisol (F) in group I was significantly lower than in group II (1.7 ± 1.1 μg/dl (8) vs. 3.6 ± 1.7 μg/d1 (21); mean ± SD (n)), and plasma F after single injection of zinc-ACTH in one group I patient tested seemed to remain at a lower level than that in group II patients. In addition, basal PAC and plasma F in 28 cases negatively correlated (γ =-0.501, p<0.01). In patients of group I and in patients of group II with high normal basal PAC, PAC was further increased after ACTH and was suppressed by Dex. However, PAC in patients of group II with low normal basal PAC equivocally responded to ACTH and Dex. PAC in 2 group I cases examined did not respond to angiotensin- II or angiotensin-III infusion.
The present results suggest that : 1) nine out of 31 patients in Japan with 17-OH-D with suppressed PRA have elevated PAC, and 2) Ald dynamics of 17-OH-D patients with high or high normal basal PAC behaves like those reported with Dex- suppressible hyperaldosteronism. A possible discrepancy of deficient 17 α -hydroxylase activities between the adrenal and gonadal glands was also suggested in 3 group II patients of 17-0H-D.
The pathophysiology of Ald secretion and the discrepancy of deficient enzyme activities in 17-OH-D patients were discussed.

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