[Isolated ACTH deficiency as a rare cause of recurrent syncope and hypoglycemia]. / Isolierter ACTH-Mangel als seltene Ursache rezidivierender Synkopen und Hypoglykämien.

HISTORY AND CLINICAL FINDINGS: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patient's behavior was slowed down and adynamic. INVESTIGATIONS: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. TREATMENT AND COURSE: Under therapy with hydrocortisone 20 mg and fludrocortisone 0.05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycemic episodes. CONCLUSION: Secondary insufficiency of the adrenal gland should be considered as a rare cause of hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin.

[Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy with octreotide]. / Monosymptomatische Hyperthyreose und TSH-produzierendes Adenom: Erfolgreiche Therapie mit Octreotid.

HISTORY AND FINDINGS: Magnetic resonance imaging (MRI) of the central nervous system was performed on a 72-year-old woman who was hyperthyroid without suppression of the thyroid-stimulating hormone (TSH) and had complained of a recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in diameter, in the anterior pituitary. The clinical symptoms were marked by a long-standing monosymptomatic illness of rapidly changing mood swings with depressive and manic phases. INVESTIGATIONS: Endocrinological-biochemical tests showed hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH: 2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a 5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified the mass as a retrosternal goitre. TREATMENT AND COURSE: As an operation on the anterior pituitary would have carried a high risk for the patient who was in a poor general condition and she had refused to be operated, treatment with octreotide, a long-acting somatostatin analogue, was initiated. This achieved a euthyroid state with partly suppressed TSH, and the patient's emotional swings ceased. CONCLUSION: If hyperthyroidism coexists with non-suppressed TSH levels, a TSH-producing hypophyseal adenoma should be considered in the differential diagnosis despite its rarity. Octreotide administration is an effective and safe treatment and is the method of choice, especially when there are contraindications to surgical resection of the anterior pituitary.

Distinct promoters induce APOBEC-1 expression in rat liver and intestine.

The expression of apolipoprotein (apo) B can be modulated by mRNA editing, a unique posttranscriptional base change in the apo B mRNA. Apo B-48, the translation product of edited apo B mRNA, is not a precursor of the atherogenic low density lipoproteins and lipoprotein(a). In humans and various other mammals, the apo B mRNA is edited in the intestine but not in the liver, which exclusively secretes apo B-100-containing lipoproteins as precursors for low density lipoprotein formation. In species such as the rat, mouse, dog, and horse, apo B mRNA is also edited in the liver, resulting in low plasma levels of low density lipoprotein. Editing of the apo B mRNA is mediated by the apo B mRNA-editing enzyme complex, of which the catalytic subunit APOBEC-1 is not expressed in the liver of species without hepatic editing. To understand the molecular basis for liver-specific expression of APOBEC-1 and the editing of hepatic apo B mRNA, the expression pattern and genomic organization of the rat APOBEC-1 gene have been characterized. The rat APOBEC-1 gene contains 6 exons and 2 promoters with distinct activities. The expression of APOBEC-1 in the rat liver is the result of a promoter located upstream, with tissue-specific exon use and alternate splicing within the 5'-untranslated region of APOBEC-1 mRNA encoded by exon 2. In addition to the liver, this promoter also induces APOBEC-1 expression in the spleen, lung, kidney, heart, and skeletal muscle. The promoter located downstream belongs to a new class of TATA-less promoters and is responsible for the abundant expression of APOBEC-1 in the intestine. Mapping of the transcriptional start sites and deletion analysis of the promoter regions by using luciferase as the reporter gene have defined the regulatory elements of both promoters. The downstream, intestine-specific promoter contains a negative regulatory element between -1100 and -500, which appears to restrict its activity to the intestine. The upstream, liver-specific promoter of the rat APOBEC-1 gene induces APOBEC-1 expression and editing of apo B mRNA in human hepatoma HuH-7 and Hep G2 cells. Understanding the molecular basis for the liver-specific expression of APOBEC-1 in the rat promises new strategies to induce APOBEC-1 expression in the human liver for the reduction of atherogenic lipoprotein levels by hepatic apo B mRNA editing.