Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy.

BACKGROUND: Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested. OBJECTIVE: The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD. PATIENTS AND METHODS: We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes. RESULTS: The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P<0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH. CONCLUSIONS: Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.

Heparin-induced thrombocytopenia in essential thrombocytosis.

We report a 67-year-old woman with essential thrombocytosis who developed cerebral infarction and heparin-induced thrombocytopenia during treatment for the cerebral infarction. She developed additional cerebral infarcts, acute femoral artery occlusion, and thrombophlebitis of her lower extremities. She was successfully treated with argatroban. This is the first report of a patient with essential thrombocytosis who developed heparin-induced thrombocytopenia and serious conditions, which included multiple thromboembolisms and coagulation disorders mimicking disseminated intravascular coagulation.

A case of primary aldosteronism caused by multiple adrenocortical macronodules.

A 60-year-old man presented with drug-resistant hypertension with hypokalemia, a high plasma aldosterone concentration (PAC) and suppressed plasma rennin activity (PRA). Imaging examinations showed multiple macronodules in the left adrenal gland. Endocrinological findings demonstrated autonomous aldosterone secretion and (131)I-adosterol scintigraphy demonstrated a left sided uptake. Laparoscopic left adrenalectomy normalized serum potassium levels and PAC, and substantially improved hypertension. Pathological and immunohistochemical analysis demonstrated that these nodules were positive for 3ß-hydroxysteroid dehydrogenase (HSD3B) but not for CYP17. In addition, zona glomerulosa demonstrated "paradoxical hyperplasia", in which these cells were negative for HSD3B. All of these data indicated that the nodules in the left adrenal gland were mainly responsible for the autonomous aldosterone secretion. We conclude that the primary aldosteronism in this case was caused by multiple macronodules. This is a very rare case of primary aldosteronism caused by multiple adrenocortical macronodules.

Growth hormone stimulates mechano growth factor expression and activates myoblast transformation in C2C12 cells.

Mechano growth factor (MGF) is an alternatively spliced variant of insulin-like growth factor-I (IGF-I). Previous reports have revealed that the MGF in skeletal muscles is induced by mechanical overload or muscle injury. In the present study, we examined the effect of growth hormone (GH) on MGF expression in C2C12 mouse muscle cell lines since GH is the principal regulator of IGF-I. The MGF mRNA increased 1 h following GH stimulation whereas IGF-IEa mRNA, which encodes a systemic type of IGF-I, increased 4 h following GH stimulation. The diverse expression of MGF and IGF-IEa was also observed in the case of muscle injury by using bupivacaine in the same cell line. Furthermore, GH induced the increase of MyoD as well as M-cadherin expression, the peak of which was parallel to that of MGF. These results indicate that GH directly and preferentially increased MGF prior to the IGF-IEa expression in C2C12 cells, which may lead to the activation of muscle satellite cells.