Fumiatsu Yakushiji

Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH receptor gene

Activating mutations of the ACTH receptor have not been previously described. We investigated a 69‐year‐old woman with normal blood cortisol but undetectable blood ACTH concentrations. The aim of this study was to evaluate her hypothalamo–pituitary–adrenal axis by measuring circadian variation in blood ACTH and cortisol, and by performing CRH and ACTH stimulation and dexamethasone suppression tests. We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis.

Primary sellar lymphoma: intravascular large B-cell lymphoma diagnosed as a double cancer and improved with chemotherapy, and literature review of primary parasellar lymphoma.

Lymphoma is one of the causative factors of hypothalamus–pituitary dysfunction, and intravascular large B-cell lymphoma (IVLBCL) is a subtype of primary extranodal neoplasm. A 69-year-old woman visited our hospital because of general fatigue. We diagnosed her with presumable non-functional primary pituitary adenoma and subsequent dysfunction. Eight months after, the patient revisited our hospital because of dyspnea. Though we conducted systemic investigations including chest and abdomen enhanced computer tomography, transbronchial lung biopsy, and bone marrow biopsy, the diagnosis was not confirmed. Inadvertently, a breast cancer was found, and the surgical specimen proved that the patient had double cancer—adenocarcinoma and IVLBCL. Rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone regimen was initiated, and complete remission was achieved. Notably, the sellar mass returned to normal size with improved function. We reviewed 32 patients with primary parasellar lymphoma. In affected sites, both sellar and pituitary stalk (6.7%), both hypothalamus and pituitary stalk (6.7%), only sellar (63.3%), only pituitary stalk (6.7%), only hypothalamus (13.3%), and only clivus (3.3%) were observed. In hypothalamus–pituitary dysfunction, both anterior and posterior dysfunction (20.7%), only anterior dysfunction (58.6%), only posterior dysfunction (3.4%), and no dysfunction (17.2%) were observed. It seemed that hypothalamic lesion is related to both anterior and posterior dysfunction, while sellar lesion is related to mainly anterior dysfunction. In cranial nerve dysfunction, 2nd nerve dysfunction (45.2%) and 6th nerve dysfunction (35.5%) were frequently observed. It seemed that sellar lesion is related to both 2nd and 6th nerve dysfunction, while hypothalamic lesion is related to mainly 2nd nerve dysfunction.

A patient with DiGeorge syndrome with spina bifida and sacral myelomeningocele, who developed both hypocalcemia-induced seizure and epilepsy

DiGeorge syndrome - a component of the 22q11 deletion syndrome - causes a disturbance in cervical neural crest migration that results in parathyroid hypoplasia. Patients can develop hypocalcemia-induced seizures. Spina bifida is caused by failure of neurulation, including a disturbance in the adhesion processes at the neurula stage. Spina bifida has been reported as a risk factor for epilepsy. We report, for the first time, the case of a patient with DiGeorge syndrome with spina bifida and sacral myelomeningocele, who developed both hypocalcemia-induced seizures and epilepsy. The patient had spina bifida and sacral myelomeningocele at birth. At the age of 13 years, he experienced a seizure for the first time. At this time, the calcium concentration was normal. An electroencephalogram (EEG) proved that the seizure was due to epilepsy. Antiepileptic medications controlled the seizure. At the age of 29, the patients calcium concentration began to reduce. At the age of 40, hypocalcemia-induced seizure occurred. At this time, the calcium concentration was 5.5mg/dL (reference range, 8.7-10.1mg/dL). The level of intact parathyroid hormone (PTH) was 6 pg/mL (reference range, 10-65 pg/mL). Chromosomal and genetic examinations revealed a deletion of TUP-like enhancer of split gene 1 (tuple1)-the diagnostic marker of DiGeorge syndrome. Many patients with DiGeorge syndrome have cardiac anomalies; however, our patient had none. We propose that the association among DiGeorge syndrome, spina bifida, epilepsy, cardiac anomaly, 22q11, tuple1, and microdeletion inheritance should be clarified for appropriate diagnosis and treatment.

Losartan potassium/hydrochlorothiazide (Preminent®) and hyponatremia: case series of 40 patients.

The clinical course of losartan potassium/hydrochlorothiazide (Preminent®)-induced hyponatremia has not been described. We summarized 40 patients with Preminent-induced hyponatremia. The study involved 15 (37.5%) men and 25 (62.5%) women (mean age [SD], 76.4 [8.3] years; range, 55–95). Their sodium levels before Preminent administration were 139.5 (4.9) mEq/L (range, 131–145; reference range, 135–147). The duration from the day of Preminent administration to the day with the lowest sodium level was 59.3 (64.9) days (range, 2–207; median, 24). Most patients for whom this duration was <50 days exhibited progressive symptoms, whereas most of those for whom this duration was >50 days did not exhibit progressive symptoms but exhibited symptoms after fever or appetite loss. The lowest sodium value was 114.4 (8.2) mEq/L (range, 99–133). The duration from the time of Preminent discontinuation to (1) the time of early recovery and (2) the time of final recovery was 6.8 (5.5) days (range, 1–20; median, 5) and 11.6 (7.6) days (range, 2–29; median, 7.5), respectively. Of the 40 patients, 36 (90.0%) achieved full recovery, 1 (2.5%) suffered from after-effects due to central pontine myelinolysis, 1 (2.5%) died, and 2 (5.0%) were unknown. In the analysis of other adverse effects of Preminent and the same adverse effects of other three angiotensin II receptor blocker (ARB)/thiazide combinations, hyponatremia was observed as a primary adverse effect of all ARB/thiazide combinations. However, hyperesthesia dermatitis was reported as an adverse effect of Preminent only.

Glutest Neo Super--a new handheld blood glucose meter-corrects for the effects of the hematocrit values in both hematocrit-adjusted samples and samples obtained from anemic patients.

BACKGROUND Handheld blood glucose (BG) meters are convenient tools that are widely used to measure the BG levels. However, the hematocrit (Hct) value has been identified as a confounding factor for accurate BG measurement. Some BG meters are equipped with an Hct-correcting feature, whose effectiveness has been tested previously. Nevertheless, the measurements yielded by many BG meters are confounded by the Hct values. Recently, a new BG meter equipped with an Hct-correcting feature has been developed; however, its effectiveness has not yet been confirmed. STUDY DESIGN Venous blood samples were collected from two healthy volunteers, and the Hct values in the samples were adjusted to approximately 0%, 10%, 20%, 30%, 40%, 50%, and 60%. Further, venous blood samples were collected from 10 anemic patients (Hct <40%). The whole BG (WBG) levels in the samples were measured using two devices-the new BG meter (Glutest Neo Super [Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan]) and a standard BG meter (OneTouch Ultra [Life Scan Inc., Milpitas, CA]). For reference, plasma glucose (PG) levels were measured using a machine at our hospital laboratory (GA08 [A&T Co., Kanagawa, Japan]). The bias in the measurements was calculated as follows: bias = ([WBG - PG]/PG) x 100. Further, the correlation between the Hct values and the bias was assessed by performing linear regression analysis. RESULTS In both the Hct-adjusted samples and the samples obtained from anemic patients, the WBG levels measured using Glutest Neo Super were minimally affected by the Hct values, while those measured using OneTouch Ultra were affected by the Hct values to a statistically significant extent. CONCLUSIONS The Hct-correcting feature of the new BG meter Glutest Neo Super was effective. The use of this new device for BG measurements may lead to more appropriate treatment selection.

Patient with isolated adrenocorticotropic hormone (ACTH) deficiency who was depressive before glucocorticoid replacement, and exhibited stupor during continuous ACTH test

HYPOAND HYPERSECRETION of the adrenocortical hormone can cause depression. However, stupor during continuous adrenocorticotropic hormone (ACTH) test has not yet been reported. In August 2010, a 56-year-old man was brought to our hospital because of general fatigue and disturbed consciousness. Laboratory examinations revealed hyponatremia (118 mEq/L) and hypoglycemia (39 mg/dL). On questioning his family, we learned that he was unsocial and frequently absented himself from work when he was in his twenties. During his forties, he isolated himself and usually locked himself in the house, and over the past 2 months, he was unable to eat by himself. On the basis of this information, we deduced that the patient was depressed. After admission, the administration of sodium and glucose improved his consciousness. Endocrinological examinations revealed normal ACTH (16.8 pg/mL, reference, 7.2–63.3 pg/ mL) and low cortisol (0.6 mg/dL, reference, 4.5–21.1 mg/dL) levels. The corticotrophin-releasing hormone test showed no response. The rapid ACTH test showed low response. Then, we performed the continuous ACTH test (tetracosactide acetate, 0.5 mg/day for 3 days). Three days later, the patient stopped talking. On the fourth day, he muttered his name many times. On the fifth day, he did not respond to speech or pain and became immobile. However, the electroencephalogram indicated that he was awake. A head computed tomography scan was normal. We consulted psychiatrists and diagnosed his condition as stupor. On the eighth day, he began to talk and move again. On the tenth day, his condition was normal without aftereffects. Before the continuous ACTH test, the urinary cortisol level was 3.6 mg/day (reference, 26.0–187.0 mg/day); on the first day of continuous ACTH test, it was 42.0 mg/day, normal response. The urinary cortisol levels on the second and third day were not measured because the patient could not collect his urine. After further examinations, we diagnosed the condition as isolated ACTH deficiency. Although results of the continuous ACTH test were not recorded on the second and third day, we suppose the stupor was caused by excessive adrenocortical hormone induced by continuous ACTH test because the effects of this test lasted for over 24 h. Thus far, only two reported patients have had adrenocortical hormone-induced stupor. Furthermore, adrenocortical insufficiency also causes stupor. Medical practitioners should be aware of the correlations between adrenocortical hormone and psychiatric symptoms. REFERENCES

Severe hypothyroidism associated with the degree of edema in a patient with nephrosis

We report the pleural fluid values of thyroid hormones and their carrier proteins in a patient who suffered from nephrotic syndrome with renal insufficiency and transient hypothyroidism. The pleural effusion was transudate. The concentrations of thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (Alb) were approximately 30–50% of the plasma. The concentrations of total triiodothyronine (TT3), total tetraiodothyronine (TT4), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) were approximately 30–50% of the plasma. Hypothyroidism was associated with the degree of edema. After improving systemic edema, proteinuria remained unchanged but the patient did not require levothyroxine. We speculate that the large amount of transudation of thyroid hormones with their carrier proteins from the blood vessels to the third space (edema and pleural effusion), thereby reducing thyroid hormones in the plasma, was associated with hypothyroidism.