Effect of low-dosage recombinant human growth hormone therapy on pulmonary function in hypopituitary patients with adult-onset growth hormone deficiency.

An impairment of the pulmonary function has been described in adult patients with childhood-onset growth hormone deficiency (GHD). We examined forced vital capacity (FVC), forced expiratory volume (FEV1), total lung capacity (TLC), functional residual capacity (FRC), residual volume (VR) and the index of inspiratory strength, middle tidal volume and tidal inspiratory time ratio (TV/I), in 29 patients with adult-onset GHD. Data were compared with those obtained in 46 healthy control subjects. Only the FEV1/FVC ratio was statistically different (p = 0.04) between the two groups of subjects. In a group of 15 GHD patients low dosages (0.5-1 IU/day s.c., bedtime) of recombinant human GH (rh-GH; n. = 8 subjects) or placebo (n. = 7) were given at random for a 6-month period. A significant increase in IGF-I levels was noted in the rh-GH-treated group (p = 0.04) but not in the placebo group. After the 6-month period no statistically significant changes in pulmonary function were found between the rh-GH-treated and placebo-treated GHD patients. This study shows that adult-onset GHD patients suffer from minimal impairment of pulmonary function. Low rh-GH dosages able to induce an increase in IGF-I levels do not improve pulmonary function. The effect of rh-GH on respiratory muscle strength could be related to the age at which GHD diagnosis is made, or induced only by high rh-GH dosages given for a long time.

The altered plasma amino acid pattern is responsible for the paradoxical growth hormone response to the oral glucose tolerance test in liver cirrhosis.

OBJECTIVE: An increased basal growth hormone (GH) secretion and a parodoxical GH response to the oral glucose tolerance test (OGTT) have been reported in patients with liver cirrhosis. It has been suggested that the ratio between branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) (BCAA/ AAA ratio) may determine in part the brain concentration of the AAAs, since the BCAAs compete with the AAAs for entry across the blood-brain barrier, leading to the accumulation of false neurotransmitters such as octopamine and phenylethanolamine, which are able to stimulate GH secretion (via alpha 2-adrenergic stimulation). In this study we investigated the role of amino acids, particularly the BCAA/AAA ratio, in the paradoxical response of GH to the OGTT in patients with liver cirrhosis. PATIENTS AND DESIGN: Twelve non-diabetic patients with biopsy-proven cirrhosis of the liver underwent an OGTT. Three of the five patients with a paradoxical response of GH to the OGTT underwent a second oral glucose administration associated with an infusion of BCAA solution from -30 min until 180 min. RESULTS: During the OGTT, glucose and insulin levels increased from 4.8 +/- 0.2 to 9.6 +/- 0.7 mmol/l (P < 0.001) and from 18.8 +/- 2.6 to 104.4 +/- 13.8 mU/l (P < 0.005), respectively. GH levels increased from 8.6 +/- 2.6 to 22.4 +/- 10.8 mU/l although not significantly. Five patients had a paradoxical GH response to the OGTT. A negative correlation between serum GH values and BCAA/AAA ratio in the plasma at every time point of the OGTT was found. After co-administration of glucose and BCAA in three patients the BCAA/AAAs ratio increased, abolishing the paradoxical GH secretion. CONCLUSIONS: Our data suggest that in liver cirrhosis the altered BCAA/AAA ratio may influence the altered basal GH secretion and the paradoxical GH response to the OGTT, probably by an increase of adrenergic mediators in the brain. Moreover, the increase of BCAA/AAA ratio seems to be able to abolish the GH paradoxical response to the OGTT.

Impact of recombinant human growth hormone treatment on psychological profiles in hypopituitary patients with adult-onset growth hormone deficiency.

BACKGROUND: We examined the effect of growth hormone (GH) administration on the psychological capacity and sense of well-being in 25 patients with adult-onset GH-deficiency (GHD). METHODS: Very low dosages [0.5-1.0 UIday(-1) s.c. at bed-time] of recombinant human (rh)-GH (n = 13; aged 50+/-15 years, mean+/-SD) or placebo (n = 12, 53+/-14 years) were given at random for a 6-month period. Quality of life was assessed by using the Italian version of the self-rating Kellner Symptom Questionnaire (KSQ) and the Hamilton Depression Scale (HDS). RESULTS: No difference in insulin-like growth factor I (IGF-I) levels was noted between groups on entry to the study. A significant increase in IGF-I [month 0 56.2+/-10.4 microg L(-1) vs. month 6 125.7+/-16.7 microg L(-1); P < 0.001] levels was noted only in the rh-GH-treated group. There was no difference in overall scores on the KSQ between the rh-GH-treated and control groups on entry. A slight, non-significant, decrease in overall scores was noted in both groups of subjects. Subsection analysis of items from the KSQ did not show significant differences in either group during the 6-month period. A significant decrease (month 0 28+/-1 vs. month 6 25+/-1; P = 0.02) in the HDS score was noted in rh-GH-treated but not in placebo-treated patients. There was a significant correlation (rs, -0.56, P = 0.05) between increase in IGF-I levels and decrease in HDS scores in rh-GH treated patients. CONCLUSION: The data demonstrate that low rh-GH dosages significantly improve psychological profiles as rated by HDS evaluation in adult-onset patients with GHD. On the other hand, a 6-month period of treatment does not produce any significant differences in quality of life as measured by KSQ between treated patients and placebo controls.

Combined cabergoline and recombinant human growth hormone treatment of an adolescent with a macroprolactinoma causing GH deficiency.

The rare macroprolactinomas seen in childhood frequently cause delayed puberty and GH deficiency. We report the combined use of cabergoline and recombinant human GH (rhGH) therapy in a male adolescent with macroprolactinoma and GH deficiency. Computed tomography and magnetic resonance imaging of the hypothalamic-pituitary region showed a macroadenoma with extrasellar extension. Neither bromocriptine nor dihydroergocryptine therapy was successful in decreasing serum PRL levels. On cabergoline treatment normal serum PRL levels were achieved within 3 months along with a marked shrinkage of the adenoma but growth rate did not increase nor did puberty start. The addition of exogenous rhGH therapy improved the growth rate, but complete pubertal development was obtained only after the administration of exogenous gonadotropins. During the combined treatment no expansion of the macroadenoma was observed. In conclusion, the combined therapy with cabergoline and rhGH seems to be safe and highly effective. Nevertheless, it warrants careful monitoring and on-going evaluation.

Coexistence of unilateral adrenal macronodule and Cushing's disease. Report of two cases.

The coexistence of an unilateral adrenal macronodule and Cushing's disease is well documented in only few reports. We hereby describe two patients with ACTH-dependent Cushing's syndrome and asymmetric adrenal involvement. In both patients the left-sided adrenal contained a nodule sized 1.5 and 1.4 cm, respectively, while the contralateral gland appeared as normal at abdominal computerized tomography. Adrenal scintiscan revealed a bilateral uptake of the tracer. Dynamic testing of hypothalamic-pituitary-adrenal axis was suggestive of pituitary dependency but neuroradiologic imaging was inconclusive. Inferior petrosal sinus sampling demonstrated a clear center to periphery ACTH gradient and an ACTH-producing pituitary microadenoma was found and removed in both cases. Hypopituitarism ensued postoperatively and Cushing's syndrome resolved but the adrenal nodules regressed only many month after operation. The present cases confirm that the presence of an adrenal mass in a patient with Cushing's syndrome is insufficient to confidently conclude for the adrenal dependency of the syndrome.