Efficacy of cabergoline on rapid escalation of dose in men with macroprolactinomas.

Background & objectives: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. Materials: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. Results: The mean age of patients at presentation was 31.7 ± 3.3 yr and duration of symptoms was 25.0 ± 3.6 months. Serum prolactin at baseline was 6249.3 ± 3259.2 μg/l with a tumour volume of 28.9 ± 8.3 cm3. Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 ± 3259.2 to 46.9 ± 14.9 μg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. Interpretation & conclusions: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

Precocious pseudopuberty with testicular enlargement.

Gonadotropins independent precocious puberty (GIPP) in male is characterized by early appearance of sexual hairs and phallic growth but without testicular enlargement. We report a case of GIPP with testicular enlargement who was diagnosed to have testotoxicosis and successfully managed with spironolactone.

Water electrolyte homeostasis in acute bronchiolitis.

Children with acute bronchiolitis frequently require hospitalization and parenteral fluid therapy. Water retention due to impaired renal water excretion has been described in several pulmonary conditions in children. We studied 20 infants (3.6 +/- 2.9 months), hospitalized consecutively for acute bronchiolitis for water and electrolyte changes during the acute stage and compared them to those on recovery. Serum sodium and plasma osmolality, urinary sodium and osmolality were measured in all infants. Ten infants each were assigned alternatively to study body water compartment or renal water handling (water load excretion and free water excretion capacity) on the day of hospitalization and after recovery. Mean ( +/- SD) value of serum sodium of the infants at admission was 132.7 +/- 7.2 mEq/L which increased to 137.1 +/- 5.4 mEq/L on recovery (p < 0.05). Plasma osmolality changed from 284 +/- 14 mOsm/kg at admission to 294 +/- 10 mOsm/kg at recovery (p < 0.05). There was a significant decrease in urinary sodium from 54 +/- 39 mEq/L to 20 +/- 18 mEq/L and urinary osmolality from 415 +/- 213 mOsm/kg to 252 +/- 204 mOsm/kg at admission and at recovery, respectively. All 10 infants showed significant increase in total body water (mean +/- SD; 22.8 +/- 7.5 ml/kg) at admission as compared to that at recovery. The total body water (TBW) excess was mainly in extracellular water compartment (16.3 +/- 3.6 ml/kg). Seven of 10 infants had significant impairment in renal water excretion. Increase in maximum free water clearance of these 7 infants on recovery was 0.69 +/- 0.27 ml/min, i.e., 15 times more than that at admission. It is concluded that bronchiolitis of infancy is characterized by water retention which is caused by impaired renal water excretion. In the management of severe bronchiolitis careful attention to fluid therapy is mandatory; liberal fluid therapy may lead to water intoxication.